ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5503C>T (p.Arg1835Ter)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5503C>T (p.Arg1835Ter)
Variation ID: 55601 Accession: VCV000055601.86
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43045767 (GRCh38) [ NCBI UCSC ] 17: 41197784 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 Oct 8, 2024 Apr 22, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.5503C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Arg1835Ter nonsense NM_001407571.1:c.5290C>T NP_001394500.1:p.Arg1764Ter nonsense NM_001407581.1:c.5569C>T NP_001394510.1:p.Arg1857Ter nonsense NM_001407582.1:c.5569C>T NP_001394511.1:p.Arg1857Ter nonsense NM_001407583.1:c.5566C>T NP_001394512.1:p.Arg1856Ter nonsense NM_001407585.1:c.5566C>T NP_001394514.1:p.Arg1856Ter nonsense NM_001407587.1:c.5566C>T NP_001394516.1:p.Arg1856Ter nonsense NM_001407590.1:c.5563C>T NP_001394519.1:p.Arg1855Ter nonsense NM_001407591.1:c.5563C>T NP_001394520.1:p.Arg1855Ter nonsense NM_001407593.1:c.5503C>T NP_001394522.1:p.Arg1835Ter nonsense NM_001407594.1:c.5503C>T NP_001394523.1:p.Arg1835Ter nonsense NM_001407596.1:c.5503C>T NP_001394525.1:p.Arg1835Ter nonsense NM_001407597.1:c.5503C>T NP_001394526.1:p.Arg1835Ter nonsense NM_001407598.1:c.5503C>T NP_001394527.1:p.Arg1835Ter nonsense NM_001407602.1:c.5503C>T NP_001394531.1:p.Arg1835Ter nonsense NM_001407603.1:c.5503C>T NP_001394532.1:p.Arg1835Ter nonsense NM_001407605.1:c.5503C>T NP_001394534.1:p.Arg1835Ter nonsense NM_001407610.1:c.5500C>T NP_001394539.1:p.Arg1834Ter nonsense NM_001407611.1:c.5500C>T NP_001394540.1:p.Arg1834Ter nonsense NM_001407612.1:c.5500C>T NP_001394541.1:p.Arg1834Ter nonsense NM_001407613.1:c.5500C>T NP_001394542.1:p.Arg1834Ter nonsense NM_001407614.1:c.5500C>T NP_001394543.1:p.Arg1834Ter nonsense NM_001407615.1:c.5500C>T NP_001394544.1:p.Arg1834Ter nonsense NM_001407616.1:c.5500C>T NP_001394545.1:p.Arg1834Ter nonsense NM_001407617.1:c.5500C>T NP_001394546.1:p.Arg1834Ter nonsense NM_001407618.1:c.5500C>T NP_001394547.1:p.Arg1834Ter nonsense NM_001407619.1:c.5500C>T NP_001394548.1:p.Arg1834Ter nonsense NM_001407620.1:c.5500C>T NP_001394549.1:p.Arg1834Ter nonsense NM_001407621.1:c.5500C>T NP_001394550.1:p.Arg1834Ter nonsense NM_001407622.1:c.5500C>T NP_001394551.1:p.Arg1834Ter nonsense NM_001407623.1:c.5500C>T NP_001394552.1:p.Arg1834Ter nonsense NM_001407624.1:c.5500C>T NP_001394553.1:p.Arg1834Ter nonsense NM_001407625.1:c.5500C>T NP_001394554.1:p.Arg1834Ter nonsense NM_001407626.1:c.5500C>T NP_001394555.1:p.Arg1834Ter nonsense NM_001407627.1:c.5497C>T NP_001394556.1:p.Arg1833Ter nonsense NM_001407628.1:c.5497C>T NP_001394557.1:p.Arg1833Ter nonsense NM_001407629.1:c.5497C>T NP_001394558.1:p.Arg1833Ter nonsense NM_001407630.1:c.5497C>T NP_001394559.1:p.Arg1833Ter nonsense NM_001407631.1:c.5497C>T NP_001394560.1:p.Arg1833Ter nonsense NM_001407632.1:c.5497C>T NP_001394561.1:p.Arg1833Ter nonsense NM_001407633.1:c.5497C>T NP_001394562.1:p.Arg1833Ter nonsense NM_001407634.1:c.5497C>T NP_001394563.1:p.Arg1833Ter nonsense NM_001407635.1:c.5497C>T NP_001394564.1:p.Arg1833Ter nonsense NM_001407636.1:c.5497C>T NP_001394565.1:p.Arg1833Ter nonsense NM_001407637.1:c.5497C>T NP_001394566.1:p.Arg1833Ter nonsense NM_001407638.1:c.5497C>T NP_001394567.1:p.Arg1833Ter nonsense NM_001407639.1:c.5497C>T NP_001394568.1:p.Arg1833Ter nonsense NM_001407640.1:c.5497C>T NP_001394569.1:p.Arg1833Ter nonsense NM_001407641.1:c.5497C>T NP_001394570.1:p.Arg1833Ter nonsense NM_001407642.1:c.5497C>T NP_001394571.1:p.Arg1833Ter nonsense NM_001407644.1:c.5494C>T NP_001394573.1:p.Arg1832Ter nonsense NM_001407645.1:c.5494C>T NP_001394574.1:p.Arg1832Ter nonsense NM_001407646.1:c.5491C>T NP_001394575.1:p.Arg1831Ter nonsense NM_001407647.1:c.5488C>T NP_001394576.1:p.Arg1830Ter nonsense NM_001407648.1:c.5446C>T NP_001394577.1:p.Arg1816Ter nonsense NM_001407649.1:c.5443C>T NP_001394578.1:p.Arg1815Ter nonsense NM_001407652.1:c.5425C>T NP_001394581.1:p.Arg1809Ter nonsense NM_001407653.1:c.5425C>T NP_001394582.1:p.Arg1809Ter nonsense NM_001407654.1:c.5425C>T NP_001394583.1:p.Arg1809Ter nonsense NM_001407655.1:c.5425C>T NP_001394584.1:p.Arg1809Ter nonsense NM_001407656.1:c.5422C>T NP_001394585.1:p.Arg1808Ter nonsense NM_001407657.1:c.5422C>T NP_001394586.1:p.Arg1808Ter nonsense NM_001407658.1:c.5422C>T NP_001394587.1:p.Arg1808Ter nonsense NM_001407659.1:c.5419C>T NP_001394588.1:p.Arg1807Ter nonsense NM_001407660.1:c.5419C>T NP_001394589.1:p.Arg1807Ter nonsense NM_001407661.1:c.5419C>T NP_001394590.1:p.Arg1807Ter nonsense NM_001407662.1:c.5419C>T NP_001394591.1:p.Arg1807Ter nonsense NM_001407663.1:c.5419C>T NP_001394592.1:p.Arg1807Ter nonsense NM_001407664.1:c.5380C>T NP_001394593.1:p.Arg1794Ter nonsense NM_001407665.1:c.5380C>T NP_001394594.1:p.Arg1794Ter nonsense NM_001407666.1:c.5380C>T NP_001394595.1:p.Arg1794Ter nonsense NM_001407667.1:c.5380C>T NP_001394596.1:p.Arg1794Ter nonsense NM_001407668.1:c.5380C>T NP_001394597.1:p.Arg1794Ter nonsense NM_001407669.1:c.5380C>T NP_001394598.1:p.Arg1794Ter nonsense NM_001407670.1:c.5377C>T NP_001394599.1:p.Arg1793Ter nonsense NM_001407671.1:c.5377C>T NP_001394600.1:p.Arg1793Ter nonsense NM_001407672.1:c.5377C>T NP_001394601.1:p.Arg1793Ter nonsense NM_001407673.1:c.5377C>T NP_001394602.1:p.Arg1793Ter nonsense NM_001407674.1:c.5377C>T NP_001394603.1:p.Arg1793Ter nonsense NM_001407675.1:c.5377C>T NP_001394604.1:p.Arg1793Ter nonsense NM_001407676.1:c.5377C>T NP_001394605.1:p.Arg1793Ter nonsense NM_001407677.1:c.5377C>T NP_001394606.1:p.Arg1793Ter nonsense NM_001407678.1:c.5377C>T NP_001394607.1:p.Arg1793Ter nonsense NM_001407679.1:c.5377C>T NP_001394608.1:p.Arg1793Ter nonsense NM_001407680.1:c.5377C>T NP_001394609.1:p.Arg1793Ter nonsense NM_001407681.1:c.5374C>T NP_001394610.1:p.Arg1792Ter nonsense NM_001407682.1:c.5374C>T NP_001394611.1:p.Arg1792Ter nonsense NM_001407683.1:c.5374C>T NP_001394612.1:p.Arg1792Ter nonsense NM_001407684.1:c.5374C>T NP_001394613.1:p.Arg1792Ter nonsense NM_001407685.1:c.5374C>T NP_001394614.1:p.Arg1792Ter nonsense NM_001407686.1:c.5374C>T NP_001394615.1:p.Arg1792Ter nonsense NM_001407687.1:c.5374C>T NP_001394616.1:p.Arg1792Ter nonsense NM_001407688.1:c.5374C>T NP_001394617.1:p.Arg1792Ter nonsense NM_001407689.1:c.5374C>T NP_001394618.1:p.Arg1792Ter nonsense NM_001407690.1:c.5371C>T NP_001394619.1:p.Arg1791Ter nonsense NM_001407691.1:c.5371C>T NP_001394620.1:p.Arg1791Ter nonsense NM_001407692.1:c.5362C>T NP_001394621.1:p.Arg1788Ter nonsense NM_001407694.1:c.5362C>T NP_001394623.1:p.Arg1788Ter nonsense NM_001407695.1:c.5362C>T NP_001394624.1:p.Arg1788Ter nonsense NM_001407696.1:c.5362C>T NP_001394625.1:p.Arg1788Ter nonsense NM_001407697.1:c.5362C>T NP_001394626.1:p.Arg1788Ter nonsense NM_001407698.1:c.5362C>T NP_001394627.1:p.Arg1788Ter nonsense NM_001407724.1:c.5362C>T NP_001394653.1:p.Arg1788Ter nonsense NM_001407725.1:c.5362C>T NP_001394654.1:p.Arg1788Ter nonsense NM_001407726.1:c.5362C>T NP_001394655.1:p.Arg1788Ter nonsense NM_001407727.1:c.5362C>T NP_001394656.1:p.Arg1788Ter nonsense NM_001407728.1:c.5362C>T NP_001394657.1:p.Arg1788Ter nonsense NM_001407729.1:c.5362C>T NP_001394658.1:p.Arg1788Ter nonsense NM_001407730.1:c.5362C>T NP_001394659.1:p.Arg1788Ter nonsense NM_001407731.1:c.5362C>T NP_001394660.1:p.Arg1788Ter nonsense NM_001407732.1:c.5359C>T NP_001394661.1:p.Arg1787Ter nonsense NM_001407733.1:c.5359C>T NP_001394662.1:p.Arg1787Ter nonsense NM_001407734.1:c.5359C>T NP_001394663.1:p.Arg1787Ter nonsense NM_001407735.1:c.5359C>T NP_001394664.1:p.Arg1787Ter nonsense NM_001407736.1:c.5359C>T NP_001394665.1:p.Arg1787Ter nonsense NM_001407737.1:c.5359C>T NP_001394666.1:p.Arg1787Ter nonsense NM_001407738.1:c.5359C>T NP_001394667.1:p.Arg1787Ter nonsense NM_001407739.1:c.5359C>T NP_001394668.1:p.Arg1787Ter nonsense NM_001407740.1:c.5359C>T NP_001394669.1:p.Arg1787Ter nonsense NM_001407741.1:c.5359C>T NP_001394670.1:p.Arg1787Ter nonsense NM_001407742.1:c.5359C>T NP_001394671.1:p.Arg1787Ter nonsense NM_001407743.1:c.5359C>T NP_001394672.1:p.Arg1787Ter nonsense NM_001407744.1:c.5359C>T NP_001394673.1:p.Arg1787Ter nonsense NM_001407745.1:c.5359C>T NP_001394674.1:p.Arg1787Ter nonsense NM_001407746.1:c.5359C>T NP_001394675.1:p.Arg1787Ter nonsense NM_001407747.1:c.5359C>T NP_001394676.1:p.Arg1787Ter nonsense NM_001407748.1:c.5359C>T NP_001394677.1:p.Arg1787Ter nonsense NM_001407749.1:c.5359C>T NP_001394678.1:p.Arg1787Ter nonsense NM_001407750.1:c.5359C>T NP_001394679.1:p.Arg1787Ter nonsense NM_001407751.1:c.5359C>T NP_001394680.1:p.Arg1787Ter nonsense NM_001407752.1:c.5359C>T NP_001394681.1:p.Arg1787Ter nonsense NM_001407838.1:c.5356C>T NP_001394767.1:p.Arg1786Ter nonsense NM_001407839.1:c.5356C>T NP_001394768.1:p.Arg1786Ter nonsense NM_001407841.1:c.5356C>T NP_001394770.1:p.Arg1786Ter nonsense NM_001407842.1:c.5356C>T NP_001394771.1:p.Arg1786Ter nonsense NM_001407843.1:c.5356C>T NP_001394772.1:p.Arg1786Ter nonsense NM_001407844.1:c.5356C>T NP_001394773.1:p.Arg1786Ter nonsense NM_001407845.1:c.5356C>T NP_001394774.1:p.Arg1786Ter nonsense NM_001407846.1:c.5356C>T NP_001394775.1:p.Arg1786Ter nonsense NM_001407847.1:c.5356C>T NP_001394776.1:p.Arg1786Ter nonsense NM_001407848.1:c.5356C>T NP_001394777.1:p.Arg1786Ter nonsense NM_001407849.1:c.5356C>T NP_001394778.1:p.Arg1786Ter nonsense NM_001407850.1:c.5356C>T NP_001394779.1:p.Arg1786Ter nonsense NM_001407851.1:c.5356C>T NP_001394780.1:p.Arg1786Ter nonsense NM_001407852.1:c.5356C>T NP_001394781.1:p.Arg1786Ter nonsense NM_001407853.1:c.5356C>T NP_001394782.1:p.Arg1786Ter nonsense NM_001407854.1:c.*17C>T NM_001407858.1:c.*17C>T NM_001407859.1:c.*17C>T NM_001407860.1:c.*17C>T NM_001407861.1:c.*17C>T NM_001407862.1:c.5302C>T NP_001394791.1:p.Arg1768Ter nonsense NM_001407863.1:c.5299C>T NP_001394792.1:p.Arg1767Ter nonsense NM_001407874.1:c.5296C>T NP_001394803.1:p.Arg1766Ter nonsense NM_001407875.1:c.5296C>T NP_001394804.1:p.Arg1766Ter nonsense NM_001407879.1:c.5293C>T NP_001394808.1:p.Arg1765Ter nonsense NM_001407881.1:c.5293C>T NP_001394810.1:p.Arg1765Ter nonsense NM_001407882.1:c.5293C>T NP_001394811.1:p.Arg1765Ter nonsense NM_001407884.1:c.5293C>T NP_001394813.1:p.Arg1765Ter nonsense NM_001407885.1:c.5293C>T NP_001394814.1:p.Arg1765Ter nonsense NM_001407886.1:c.5293C>T NP_001394815.1:p.Arg1765Ter nonsense NM_001407887.1:c.5293C>T NP_001394816.1:p.Arg1765Ter nonsense NM_001407889.1:c.5293C>T NP_001394818.1:p.Arg1765Ter nonsense NM_001407894.1:c.5290C>T NP_001394823.1:p.Arg1764Ter nonsense NM_001407895.1:c.5290C>T NP_001394824.1:p.Arg1764Ter nonsense NM_001407896.1:c.5290C>T NP_001394825.1:p.Arg1764Ter nonsense NM_001407897.1:c.5290C>T NP_001394826.1:p.Arg1764Ter nonsense NM_001407898.1:c.5290C>T NP_001394827.1:p.Arg1764Ter nonsense NM_001407899.1:c.5290C>T NP_001394828.1:p.Arg1764Ter nonsense NM_001407900.1:c.5290C>T NP_001394829.1:p.Arg1764Ter nonsense NM_001407902.1:c.5290C>T NP_001394831.1:p.Arg1764Ter nonsense NM_001407904.1:c.5290C>T NP_001394833.1:p.Arg1764Ter nonsense NM_001407906.1:c.5290C>T NP_001394835.1:p.Arg1764Ter nonsense NM_001407907.1:c.5290C>T NP_001394836.1:p.Arg1764Ter nonsense NM_001407908.1:c.5290C>T NP_001394837.1:p.Arg1764Ter nonsense NM_001407909.1:c.5290C>T NP_001394838.1:p.Arg1764Ter nonsense NM_001407910.1:c.5290C>T NP_001394839.1:p.Arg1764Ter nonsense NM_001407915.1:c.5287C>T NP_001394844.1:p.Arg1763Ter nonsense NM_001407916.1:c.5287C>T NP_001394845.1:p.Arg1763Ter nonsense NM_001407917.1:c.5287C>T NP_001394846.1:p.Arg1763Ter nonsense NM_001407918.1:c.5287C>T NP_001394847.1:p.Arg1763Ter nonsense NM_001407919.1:c.5251C>T NP_001394848.1:p.Arg1751Ter nonsense NM_001407920.1:c.5239C>T NP_001394849.1:p.Arg1747Ter nonsense NM_001407921.1:c.5239C>T NP_001394850.1:p.Arg1747Ter nonsense NM_001407922.1:c.5239C>T NP_001394851.1:p.Arg1747Ter nonsense NM_001407923.1:c.5239C>T NP_001394852.1:p.Arg1747Ter nonsense NM_001407924.1:c.5239C>T NP_001394853.1:p.Arg1747Ter nonsense NM_001407925.1:c.5239C>T NP_001394854.1:p.Arg1747Ter nonsense NM_001407926.1:c.5239C>T NP_001394855.1:p.Arg1747Ter nonsense NM_001407927.1:c.5236C>T NP_001394856.1:p.Arg1746Ter nonsense NM_001407928.1:c.5236C>T NP_001394857.1:p.Arg1746Ter nonsense NM_001407929.1:c.5236C>T NP_001394858.1:p.Arg1746Ter nonsense NM_001407930.1:c.5236C>T NP_001394859.1:p.Arg1746Ter nonsense NM_001407931.1:c.5236C>T NP_001394860.1:p.Arg1746Ter nonsense NM_001407932.1:c.5236C>T NP_001394861.1:p.Arg1746Ter nonsense NM_001407933.1:c.5236C>T NP_001394862.1:p.Arg1746Ter nonsense NM_001407934.1:c.5233C>T NP_001394863.1:p.Arg1745Ter nonsense NM_001407935.1:c.5233C>T NP_001394864.1:p.Arg1745Ter nonsense NM_001407936.1:c.5233C>T NP_001394865.1:p.Arg1745Ter nonsense NM_001407937.1:c.*17C>T NM_001407938.1:c.*17C>T NM_001407939.1:c.*17C>T NM_001407940.1:c.*17C>T NM_001407941.1:c.*17C>T NM_001407942.1:c.*17C>T NM_001407943.1:c.*17C>T NM_001407944.1:c.*17C>T NM_001407945.1:c.*17C>T NM_001407946.1:c.5170C>T NP_001394875.1:p.Arg1724Ter nonsense NM_001407947.1:c.5170C>T NP_001394876.1:p.Arg1724Ter nonsense NM_001407948.1:c.5170C>T NP_001394877.1:p.Arg1724Ter nonsense NM_001407949.1:c.5170C>T NP_001394878.1:p.Arg1724Ter nonsense NM_001407950.1:c.5167C>T NP_001394879.1:p.Arg1723Ter nonsense NM_001407951.1:c.5167C>T NP_001394880.1:p.Arg1723Ter nonsense NM_001407952.1:c.5167C>T NP_001394881.1:p.Arg1723Ter nonsense NM_001407953.1:c.5167C>T NP_001394882.1:p.Arg1723Ter nonsense NM_001407954.1:c.5167C>T NP_001394883.1:p.Arg1723Ter nonsense NM_001407955.1:c.5167C>T NP_001394884.1:p.Arg1723Ter nonsense NM_001407956.1:c.5164C>T NP_001394885.1:p.Arg1722Ter nonsense NM_001407957.1:c.5164C>T NP_001394886.1:p.Arg1722Ter nonsense NM_001407958.1:c.5164C>T NP_001394887.1:p.Arg1722Ter nonsense NM_001407959.1:c.5122C>T NP_001394888.1:p.Arg1708Ter nonsense NM_001407960.1:c.5119C>T NP_001394889.1:p.Arg1707Ter nonsense NM_001407962.1:c.5119C>T NP_001394891.1:p.Arg1707Ter nonsense NM_001407963.1:c.5116C>T NP_001394892.1:p.Arg1706Ter nonsense NM_001407964.1:c.5041C>T NP_001394893.1:p.Arg1681Ter nonsense NM_001407965.1:c.4996C>T NP_001394894.1:p.Arg1666Ter nonsense NM_001407966.1:c.4615C>T NP_001394895.1:p.Arg1539Ter nonsense NM_001407967.1:c.4612C>T NP_001394896.1:p.Arg1538Ter nonsense NM_001407968.1:c.2899C>T NP_001394897.1:p.Arg967Ter nonsense NM_001407969.1:c.2896C>T NP_001394898.1:p.Arg966Ter nonsense NM_001407970.1:c.2260C>T NP_001394899.1:p.Arg754Ter nonsense NM_001407971.1:c.2260C>T NP_001394900.1:p.Arg754Ter nonsense NM_001407972.1:c.2257C>T NP_001394901.1:p.Arg753Ter nonsense NM_001407973.1:c.2194C>T NP_001394902.1:p.Arg732Ter nonsense NM_001407974.1:c.2194C>T NP_001394903.1:p.Arg732Ter nonsense NM_001407975.1:c.2194C>T NP_001394904.1:p.Arg732Ter nonsense NM_001407976.1:c.2194C>T NP_001394905.1:p.Arg732Ter nonsense NM_001407977.1:c.2194C>T NP_001394906.1:p.Arg732Ter nonsense NM_001407978.1:c.2194C>T NP_001394907.1:p.Arg732Ter nonsense NM_001407979.1:c.2191C>T NP_001394908.1:p.Arg731Ter nonsense NM_001407980.1:c.2191C>T NP_001394909.1:p.Arg731Ter nonsense NM_001407981.1:c.2191C>T NP_001394910.1:p.Arg731Ter nonsense NM_001407982.1:c.2191C>T NP_001394911.1:p.Arg731Ter nonsense NM_001407983.1:c.2191C>T NP_001394912.1:p.Arg731Ter nonsense NM_001407984.1:c.2191C>T NP_001394913.1:p.Arg731Ter nonsense NM_001407985.1:c.2191C>T NP_001394914.1:p.Arg731Ter nonsense NM_001407986.1:c.2191C>T NP_001394915.1:p.Arg731Ter nonsense NM_001407990.1:c.2191C>T NP_001394919.1:p.Arg731Ter nonsense NM_001407991.1:c.2191C>T NP_001394920.1:p.Arg731Ter nonsense NM_001407992.1:c.2191C>T NP_001394921.1:p.Arg731Ter nonsense NM_001407993.1:c.2191C>T NP_001394922.1:p.Arg731Ter nonsense NM_001408392.1:c.2188C>T NP_001395321.1:p.Arg730Ter nonsense NM_001408396.1:c.2188C>T NP_001395325.1:p.Arg730Ter nonsense NM_001408397.1:c.2188C>T NP_001395326.1:p.Arg730Ter nonsense NM_001408398.1:c.2188C>T NP_001395327.1:p.Arg730Ter nonsense NM_001408399.1:c.2188C>T NP_001395328.1:p.Arg730Ter nonsense NM_001408400.1:c.2188C>T NP_001395329.1:p.Arg730Ter nonsense NM_001408401.1:c.2188C>T NP_001395330.1:p.Arg730Ter nonsense NM_001408402.1:c.2188C>T NP_001395331.1:p.Arg730Ter nonsense NM_001408403.1:c.2188C>T NP_001395332.1:p.Arg730Ter nonsense NM_001408404.1:c.2188C>T NP_001395333.1:p.Arg730Ter nonsense NM_001408406.1:c.2185C>T NP_001395335.1:p.Arg729Ter nonsense NM_001408407.1:c.2185C>T NP_001395336.1:p.Arg729Ter nonsense NM_001408408.1:c.2185C>T NP_001395337.1:p.Arg729Ter nonsense NM_001408409.1:c.2182C>T NP_001395338.1:p.Arg728Ter nonsense NM_001408410.1:c.2119C>T NP_001395339.1:p.Arg707Ter nonsense NM_001408411.1:c.2116C>T NP_001395340.1:p.Arg706Ter nonsense NM_001408412.1:c.2113C>T NP_001395341.1:p.Arg705Ter nonsense NM_001408413.1:c.2113C>T NP_001395342.1:p.Arg705Ter nonsense NM_001408414.1:c.2113C>T NP_001395343.1:p.Arg705Ter nonsense NM_001408415.1:c.2113C>T NP_001395344.1:p.Arg705Ter nonsense NM_001408416.1:c.2113C>T NP_001395345.1:p.Arg705Ter nonsense NM_001408418.1:c.2077C>T NP_001395347.1:p.Arg693Ter nonsense NM_001408419.1:c.2077C>T NP_001395348.1:p.Arg693Ter nonsense NM_001408420.1:c.2077C>T NP_001395349.1:p.Arg693Ter nonsense NM_001408421.1:c.2074C>T NP_001395350.1:p.Arg692Ter nonsense NM_001408422.1:c.2074C>T NP_001395351.1:p.Arg692Ter nonsense NM_001408423.1:c.2074C>T NP_001395352.1:p.Arg692Ter nonsense NM_001408424.1:c.2074C>T NP_001395353.1:p.Arg692Ter nonsense NM_001408425.1:c.2071C>T NP_001395354.1:p.Arg691Ter nonsense NM_001408426.1:c.2071C>T NP_001395355.1:p.Arg691Ter nonsense NM_001408427.1:c.2071C>T NP_001395356.1:p.Arg691Ter nonsense NM_001408428.1:c.2071C>T NP_001395357.1:p.Arg691Ter nonsense NM_001408429.1:c.2071C>T NP_001395358.1:p.Arg691Ter nonsense NM_001408430.1:c.2071C>T NP_001395359.1:p.Arg691Ter nonsense NM_001408431.1:c.2071C>T NP_001395360.1:p.Arg691Ter nonsense NM_001408432.1:c.2068C>T NP_001395361.1:p.Arg690Ter nonsense NM_001408433.1:c.2068C>T NP_001395362.1:p.Arg690Ter nonsense NM_001408434.1:c.2068C>T NP_001395363.1:p.Arg690Ter nonsense NM_001408435.1:c.2068C>T NP_001395364.1:p.Arg690Ter nonsense NM_001408436.1:c.2068C>T NP_001395365.1:p.Arg690Ter nonsense NM_001408437.1:c.2068C>T NP_001395366.1:p.Arg690Ter nonsense NM_001408438.1:c.2068C>T NP_001395367.1:p.Arg690Ter nonsense NM_001408439.1:c.2068C>T NP_001395368.1:p.Arg690Ter nonsense NM_001408440.1:c.2068C>T NP_001395369.1:p.Arg690Ter nonsense NM_001408441.1:c.2068C>T NP_001395370.1:p.Arg690Ter nonsense NM_001408442.1:c.2068C>T NP_001395371.1:p.Arg690Ter nonsense NM_001408443.1:c.2068C>T NP_001395372.1:p.Arg690Ter nonsense NM_001408444.1:c.2068C>T NP_001395373.1:p.Arg690Ter nonsense NM_001408445.1:c.2065C>T NP_001395374.1:p.Arg689Ter nonsense NM_001408446.1:c.2065C>T NP_001395375.1:p.Arg689Ter nonsense NM_001408447.1:c.2065C>T NP_001395376.1:p.Arg689Ter nonsense NM_001408448.1:c.2065C>T NP_001395377.1:p.Arg689Ter nonsense NM_001408450.1:c.2065C>T NP_001395379.1:p.Arg689Ter nonsense NM_001408451.1:c.2059C>T NP_001395380.1:p.Arg687Ter nonsense NM_001408452.1:c.2053C>T NP_001395381.1:p.Arg685Ter nonsense NM_001408453.1:c.2053C>T NP_001395382.1:p.Arg685Ter nonsense NM_001408454.1:c.2053C>T NP_001395383.1:p.Arg685Ter nonsense NM_001408455.1:c.2053C>T NP_001395384.1:p.Arg685Ter nonsense NM_001408456.1:c.2053C>T NP_001395385.1:p.Arg685Ter nonsense NM_001408457.1:c.2053C>T NP_001395386.1:p.Arg685Ter nonsense NM_001408458.1:c.2050C>T NP_001395387.1:p.Arg684Ter nonsense NM_001408459.1:c.2050C>T NP_001395388.1:p.Arg684Ter nonsense NM_001408460.1:c.2050C>T NP_001395389.1:p.Arg684Ter nonsense NM_001408461.1:c.2050C>T NP_001395390.1:p.Arg684Ter nonsense NM_001408462.1:c.2050C>T NP_001395391.1:p.Arg684Ter nonsense NM_001408463.1:c.2050C>T NP_001395392.1:p.Arg684Ter nonsense NM_001408464.1:c.2050C>T NP_001395393.1:p.Arg684Ter nonsense NM_001408465.1:c.2050C>T NP_001395394.1:p.Arg684Ter nonsense NM_001408466.1:c.2050C>T NP_001395395.1:p.Arg684Ter nonsense NM_001408467.1:c.2050C>T NP_001395396.1:p.Arg684Ter nonsense NM_001408468.1:c.2047C>T NP_001395397.1:p.Arg683Ter nonsense NM_001408469.1:c.2047C>T NP_001395398.1:p.Arg683Ter nonsense NM_001408470.1:c.2047C>T NP_001395399.1:p.Arg683Ter nonsense NM_001408472.1:c.*17C>T NM_001408473.1:c.*17C>T NM_001408474.1:c.1993C>T NP_001395403.1:p.Arg665Ter nonsense NM_001408475.1:c.1990C>T NP_001395404.1:p.Arg664Ter nonsense NM_001408476.1:c.1990C>T NP_001395405.1:p.Arg664Ter nonsense NM_001408478.1:c.1984C>T NP_001395407.1:p.Arg662Ter nonsense NM_001408479.1:c.1984C>T NP_001395408.1:p.Arg662Ter nonsense NM_001408480.1:c.1984C>T NP_001395409.1:p.Arg662Ter nonsense NM_001408481.1:c.1981C>T NP_001395410.1:p.Arg661Ter nonsense NM_001408482.1:c.1981C>T NP_001395411.1:p.Arg661Ter nonsense NM_001408483.1:c.1981C>T NP_001395412.1:p.Arg661Ter nonsense NM_001408484.1:c.1981C>T NP_001395413.1:p.Arg661Ter nonsense NM_001408485.1:c.1981C>T NP_001395414.1:p.Arg661Ter nonsense NM_001408489.1:c.1981C>T NP_001395418.1:p.Arg661Ter nonsense NM_001408490.1:c.1981C>T NP_001395419.1:p.Arg661Ter nonsense NM_001408491.1:c.1981C>T NP_001395420.1:p.Arg661Ter nonsense NM_001408492.1:c.1978C>T NP_001395421.1:p.Arg660Ter nonsense NM_001408493.1:c.1978C>T NP_001395422.1:p.Arg660Ter nonsense NM_001408494.1:c.1954C>T NP_001395423.1:p.Arg652Ter nonsense NM_001408495.1:c.1948C>T NP_001395424.1:p.Arg650Ter nonsense NM_001408496.1:c.1930C>T NP_001395425.1:p.Arg644Ter nonsense NM_001408497.1:c.1930C>T NP_001395426.1:p.Arg644Ter nonsense NM_001408498.1:c.1930C>T NP_001395427.1:p.Arg644Ter nonsense NM_001408499.1:c.1930C>T NP_001395428.1:p.Arg644Ter nonsense NM_001408500.1:c.1930C>T NP_001395429.1:p.Arg644Ter nonsense NM_001408501.1:c.1930C>T NP_001395430.1:p.Arg644Ter nonsense NM_001408502.1:c.1927C>T NP_001395431.1:p.Arg643Ter nonsense NM_001408503.1:c.1927C>T NP_001395432.1:p.Arg643Ter nonsense NM_001408504.1:c.1927C>T NP_001395433.1:p.Arg643Ter nonsense NM_001408505.1:c.1924C>T NP_001395434.1:p.Arg642Ter nonsense NM_001408506.1:c.1867C>T NP_001395435.1:p.Arg623Ter nonsense NM_001408507.1:c.1864C>T NP_001395436.1:p.Arg622Ter nonsense NM_001408508.1:c.1855C>T NP_001395437.1:p.Arg619Ter nonsense NM_001408509.1:c.1852C>T NP_001395438.1:p.Arg618Ter nonsense NM_001408510.1:c.1813C>T NP_001395439.1:p.Arg605Ter nonsense NM_001408511.1:c.1810C>T NP_001395440.1:p.Arg604Ter nonsense NM_001408512.1:c.1690C>T NP_001395441.1:p.Arg564Ter nonsense NM_001408513.1:c.1663C>T NP_001395442.1:p.Arg555Ter nonsense NM_001408514.1:c.1267C>T NP_001395443.1:p.Arg423Ter nonsense NM_007297.4:c.5362C>T NP_009228.2:p.Arg1788Ter nonsense NM_007298.4:c.2191C>T NP_009229.2:p.Arg731Ter nonsense NM_007299.4:c.*17C>T 3 prime UTR NM_007300.4:c.5566C>T NP_009231.2:p.Arg1856Ter nonsense NM_007304.2:c.2191C>T NP_009235.2:p.Arg731Ter nonsense NR_027676.2:n.5680C>T non-coding transcript variant NC_000017.11:g.43045767G>A NC_000017.10:g.41197784G>A NG_005905.2:g.172217C>T LRG_292:g.172217C>T LRG_292t1:c.5503C>T LRG_292p1:p.Arg1835Ter U14680.1:n.5622C>T - Protein change
- R1835*, R1856*, R1788*, R731*, R1539*, R1681*, R1706*, R1708*, R1764*, R1808*, R1809*, R1857*, R604*, R605*, R644*, R661*, R687*, R689*, R705*, R753*, R754*, R1666*, R1722*, R1723*, R1745*, R1747*, R1763*, R1766*, R1767*, R1807*, R1816*, R1831*, R1834*, R555*, R564*, R619*, R622*, R623*, R652*, R683*, R684*, R691*, R693*, R706*, R1538*, R1707*, R1724*, R1765*, R1787*, R1791*, R1793*, R1794*, R1815*, R1830*, R1855*, R618*, R642*, R643*, R660*, R662*, R664*, R685*, R729*, R966*, R1746*, R1751*, R1768*, R1786*, R1792*, R1832*, R1833*, R423*, R650*, R665*, R690*, R692*, R707*, R728*, R730*, R732*, R967*
- Other names
- p.R1835*:CGA>TGA
- 5622C>T
- Canonical SPDI
- NC_000017.11:43045766:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- functionally_abnormal Sequence Ontology [SO:0002218]
- The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5503C>T, a NONSENSE variant, produced a function score of -2.3, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute, University of Washington]
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD), exomes 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13037 | 14843 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (11) |
criteria provided, multiple submitters, no conflicts
|
Nov 17, 2023 | RCV000049020.53 | |
Pathogenic (18) |
reviewed by expert panel
|
Apr 22, 2016 | RCV000077627.36 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Feb 7, 2023 | RCV000131862.21 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV000203652.28 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jan 1, 2020 | RCV000238956.11 | |
Pathogenic (1) |
criteria provided, single submitter
|
Nov 1, 2015 | RCV000240766.9 | |
Pathogenic (2) |
criteria provided, single submitter
|
Sep 21, 2015 | RCV000735447.11 | |
Pathogenic (1) |
no assertion criteria provided
|
Dec 1, 2018 | RCV000785213.10 | |
Pathogenic (1) |
no assertion criteria provided
|
- | RCV001353835.9 | |
Pathogenic (1) |
no assertion criteria provided
|
Aug 8, 2021 | RCV001554249.9 | |
Pathogenic (1) |
no assertion criteria provided
|
Mar 19, 2021 | RCV001527479.9 | |
Pathogenic (1) |
no assertion criteria provided
|
Jul 1, 2021 | RCV003162421.8 | |
Pathogenic (1) |
criteria provided, single submitter
|
Sep 29, 2021 | RCV002496720.8 | |
click to load more click to collapse |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Apr 22, 2016)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000282345.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
Pathogenic
(Nov 01, 2015)
|
criteria provided, single submitter
Method: research
|
Breast neoplasm
Affected status: yes
Allele origin:
somatic
|
Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University
Additional submitter:
Asia and Emerging Markets iMed, AstraZeneca
Accession: SCV000265868.1
First in ClinVar: Sep 14, 2016 Last updated: Sep 14, 2016 |
Number of individuals with the variant: 1
Geographic origin: China
|
|
Pathogenic
(Sep 21, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Study: Canadian Open Genetics Repository
Accession: SCV000324836.2 First in ClinVar: Jul 01, 2016 Last updated: May 06, 2019 |
|
|
Pathogenic
(Dec 08, 2020)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002537868.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The BRCA1 c.5503C>T (p.R1835X) variant has been reported in several individuals with breast and/or ovarian cancer (PMID: 24504028, 27553291). Functional studies have shown that this … (more)
The BRCA1 c.5503C>T (p.R1835X) variant has been reported in several individuals with breast and/or ovarian cancer (PMID: 24504028, 27553291). Functional studies have shown that this variant alters the protein function (PMID: 30209399). As this variant is not predicted to cause nonsense-mediated decay, the protein product is expected to be truncated. This variant was observed in 2/30616 chromosomes in the South Asian (SAS) population, according to the Genome Aggregation Database (PMID: 27535533). Based on the current evidence available, this variant is interpreted as pathogenic. (less)
|
|
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Pathogenic
(Oct 02, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000326344.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
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Pathogenic
(Sep 14, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004216909.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
Pathogenic
(Feb 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000537638.4
First in ClinVar: Mar 24, 2017 Last updated: Feb 14, 2024 |
Comment:
This variant changes 1 nucleotide in exon 23 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 23 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported to result in the loss of BRCA1 protein function in a haploid cell proliferation assay (PMID: 30209399). This variant has been reported in more than twenty individuals affected with breast and/or ovarian cancer (PMID: 8554067, 9760198, 10505028, 11260866, 16644204, 16683254, 20104584, 20727672, 24504028, 24549055, 25682074, 26187060, 26541979, 27153395, 27553291, 28324225, 28423363, 28724667, 29339979, 29470806, 31209999) and has been identified in over 100 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant has been identified in 3/251278 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
|
|
Pathogenic
(Feb 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000186917.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.R1835* pathogenic mutation (also known as c.5503C>T), located in coding exon 22 of the BRCA1 gene, results from a C to T substitution at … (more)
The p.R1835* pathogenic mutation (also known as c.5503C>T), located in coding exon 22 of the BRCA1 gene, results from a C to T substitution at nucleotide position 5503. This changes the amino acid from an arginine to a stop codon within coding exon 22. This alteration occurs at the 3' terminus of theBRCA1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 29 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This mutation has been detected in multiple hereditary breast and ovarian cancer (HBOC) syndrome cohorts to date (Serova O et al. Am. J. Hum. Genet. 1996 Jan;58:42-51; Rashid MU et al. BMC Cancer. 2016 08;16:673; Meisel C et al. Arch. Gynecol. Obstet. 2017 May;295:1227-1238; Briceño-Balcázar I et al. Colomb. Med. 2017 Jun;48:58-63; Sun J et al. Clin. Cancer Res. 2017 Oct;23:6113-6119; Heramb C et al. Hered. Cancer Clin. Pract. 2018 Jan;16:3; Apessos A et al. Cancer Genet. 2018 01;220:1-12). One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). Of note, this alteration is also designated as 5622C>T in published literature. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
|
|
Pathogenic
(May 27, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Accession: SCV005045937.1
First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024 |
Comment:
PVS1; PM5_PTC_Strong
|
|
Pathogenic
(Jul 01, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Medical Genetics, Oslo University Hospital
Accession: SCV000564353.1
First in ClinVar: Apr 22, 2017 Last updated: Apr 22, 2017 |
Number of individuals with the variant: 6
|
|
Pathogenic
(Oct 08, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743370.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
Pathogenic
(Sep 21, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744581.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
Pathogenic
(Nov 28, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000806977.1
First in ClinVar: Sep 13, 2018 Last updated: Sep 13, 2018 |
|
|
Pathogenic
(Jan 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary Breast Carcinoma
Affected status: yes
Allele origin:
germline
|
GeneKor MSA
Accession: SCV000296784.3
First in ClinVar: Aug 01, 2016 Last updated: Apr 24, 2020 |
Comment:
This variant is a single amino acid change from Arginine to a termination codon at amino acid residue 1835 of the BRCA1 gene. It is … (more)
This variant is a single amino acid change from Arginine to a termination codon at amino acid residue 1835 of the BRCA1 gene. It is expected to result in a truncated, non-functional protein. Truncating variants in BRCA1 are known to be pathogenic. (less)
|
|
Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446590.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Sex: female
|
|
Pathogenic
(Apr 10, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001449724.1
First in ClinVar: Dec 10, 2020 Last updated: Dec 10, 2020 |
Number of individuals with the variant: 1
|
|
Pathogenic
(Dec 28, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699267.2
First in ClinVar: Dec 26, 2017 Last updated: Jan 09, 2021 |
Comment:
Variant summary: BRCA1 c.5503C>T (p.Arg1835X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA1 c.5503C>T (p.Arg1835X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.2e-05 in 251278 control chromosomes. c.5503C>T has been widely reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple clinical diagnostic laboratories and one expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
Pathogenic
(Jan 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002070456.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
Comment:
DNA sequence analysis of the BRCA1 gene demonstrated a sequence change, c.5503C>T, which results in the creation of a premature stop codon at amino acid … (more)
DNA sequence analysis of the BRCA1 gene demonstrated a sequence change, c.5503C>T, which results in the creation of a premature stop codon at amino acid position 1835, p.Arg1835*. This sequence change is reported in the gnomAD database with a global population frequency of 0.0012% (dbSNP rs41293465). This sequence change has been described in multiple individuals and families with breast, ovarian and bladder cancer (PMID: 27553291, 8554067, 10486320,11802209, 16683254,19949876, 23704984,31528241). Of note, this alteration is also designated as 5622C>T in published literature. Functional studies have shown that although this variant does not trigger nonsense-mediated mRNA decay (PMID: 12393792), it results in a truncated protein lacking the last few amino acid residues and displayed loss of activity (PMID: 11157798). These collective evidences indicate that this sequence change is pathogenic. (less)
|
|
Likely pathogenic
(Nov 14, 2014)
|
criteria provided, single submitter
Method: literature only
|
Breast-ovarian cancer, familial 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000220880.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
|
|
Pathogenic
(Sep 29, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Breast-ovarian cancer, familial, susceptibility to, 1 Pancreatic cancer, susceptibility to, 4 Fanconi anemia, complementation group S
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002809035.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Pathogenic
(Jun 09, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000210227.16
First in ClinVar: Feb 24, 2015 Last updated: Jun 17, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation in a gene for which loss of function is a known mechanism of disease; Reported in association … (more)
Nonsense variant predicted to result in protein truncation in a gene for which loss of function is a known mechanism of disease; Reported in association with hereditary breast and/or ovarian cancer (Serova et al., 1996; Meindl, 2002; Rashid et al., 2006; van der Hout et al., 2006; Borg et al., 2010; Cunningham et al., 2014; Kwong et al., 2016); Published functional studies demonstrate a damaging effect: variant classified as non-functional based on a saturation genome editing (SGE) assay measuring cell survival (Findlay et al., 2018); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 5622C>T; This variant is associated with the following publications: (PMID: 12360400, 24504028, 16998791, 29176636, 8554067, 25682074, 26541979, 25085752, 26898890, 26848529, 21559243, 17591843, 11260866, 9796975, 27767231, 25066507, 16683254, 27553291, 15026808, 29922827, 28888541, 34282142, 20727672, 26404129, 10505028, 18465347, 10486320, 26028024, 25722380, 27157322, 12601471, 12960223, 18375895, 11920621, 16782705, 12393792, 24578176, 9760198, 20104584, 24728189, 27194814, 23569316, 16644204, 11739404, 11802209, 9667259, 10699917, 16528604, 26976419, 24249303, 19949876, 23704984, 28324225, 29339979, 29752822, 29470806, 28724667, 28993434, 29310832, 30702160, 29446198, 31090900, 31528241, 30855176, 30291343, 32338768, 33758026, 35356428, 33804961, 35377489, 33087929, 30875412, 32710294, 32719484, 31825140, 33654310, 36988593, 30209399) (less)
|
|
Pathogenic
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002009419.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
|
|
Pathogenic
(Sep 13, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004034290.1
First in ClinVar: Sep 16, 2023 Last updated: Sep 16, 2023 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg1856*) in the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Arg1856*) in the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 29 amino acid(s) of the BRCA1 protein. This variant is present in population databases (rs41293465, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with breast, ovarian, and bladder cancer (PMID: 8554067, 10486320, 11802209, 16683254, 19949876, 23704984, 27553291). This variant is also known as 5622C>T. ClinVar contains an entry for this variant (Variation ID: 55601). Functional studies have shown that although this variant does not trigger nonsense-mediated mRNA decay (PMID: 12393792), it results in a truncated protein lacking the last few amino acid residues and displayed loss of activity (PMID: 11157798). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
Age: 40-49 years
Sex: female
|
|
Pathogenic
(Nov 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004027747.2
First in ClinVar: Aug 26, 2023 Last updated: Dec 17, 2023 |
Comment:
Criteria applied: PVS1,PS3,PM5_PTC
Clinical Features:
Family history of cancer (present)
Sex: female
|
|
Pathogenic
(Feb 20, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296284.5
First in ClinVar: Jun 24, 2016 Last updated: Jan 06, 2024 |
Comment:
This nonsense variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been reported in multiple individuals with breast and/or ovarian cancer … (more)
This nonsense variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been reported in multiple individuals with breast and/or ovarian cancer in the published literature (PMID: 8554067 (1996), 16998791 (2006), 24504028 (2014), 27553291 (2016), 29021639 (2017), 28724667 (2017)). Based on the available information, this variant is classified as pathogenic. (less)
|
|
Pathogenic
(Nov 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002024700.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000077033.14
First in ClinVar: Jul 03, 2013 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg1835*) in the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Arg1835*) in the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 29 amino acid(s) of the BRCA1 protein. This variant is present in population databases (rs41293465, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with breast, ovarian, and bladder cancer (PMID: 8554067, 10486320, 11802209, 16683254, 19949876, 23704984, 27553291). This variant is also known as 5622C>T. ClinVar contains an entry for this variant (Variation ID: 55601). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects BRCA1 function (PMID: 11739404). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). This variant disrupts a region of the BRCA1 protein in which other variant(s) (p.Tyr1853*) have been determined to be pathogenic (PMID: 12400015, 21922593; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Jan 08, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004817536.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
This variant changes 1 nucleotide in exon 23 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 23 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported to result in the loss of BRCA1 protein function in a haploid cell proliferation assay (PMID: 30209399). This variant has been reported in more than twenty individuals affected with breast and/or ovarian cancer (PMID: 8554067, 9760198, 10505028, 11260866, 16644204, 16683254, 20104584, 20727672, 24504028, 24549055, 25682074, 26187060, 26541979, 27153395, 27553291, 28324225, 28423363, 28724667, 29339979, 29470806, 31209999) and has been identified in over 100 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant has been identified in 3/251278 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
Number of individuals with the variant: 5
|
|
Pathogenic
(May 08, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004848012.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Arg1835X variant in BRCA1 has been identified in >50 individuals with BRCA1-associated cancers (Breast Cancer Information Core (BIC) database). This variant has been identified … (more)
The p.Arg1835X variant in BRCA1 has been identified in >50 individuals with BRCA1-associated cancers (Breast Cancer Information Core (BIC) database). This variant has been identified in 2/30616 South Asian chromosomes by the Genome Aggregation Database (GnomAD, http://gnomad.broadinstitute.org); however, this frequency is low enough to be consistent with the frequency of hereditary breast and ovarian cancer (HBOC) in the general population. This nonsense variant leads to a premature termination codon at position 1835. This alteration occurs within the last exon and is more likely to escape nonsense mediated decay (NMD), resulting in a truncated protein. However, in vitro functional studies provide some evidence that this truncation may impact protein function (Ye 2001). Furthermore, this variant was classified as Pathogenic on Apr 22, 2016 by the ClinGen-approved ENIGMA Expert Panel (ClinVar SCV000282345.1). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant hereditary breast and ovarian cancer (HBOC) based upon its frequency in affected individuals and absence from controls. ACMG/AMP Criteria applied: PVS1_Strong, PS4, PS3_Supporting, PM2. (less)
|
|
Pathogenic
(Jul 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247339.25
First in ClinVar: May 09, 2020 Last updated: Oct 08, 2024 |
Comment:
BRCA1: PVS1, PM2, PS3:Supporting
Number of individuals with the variant: 3
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV005044822.2
First in ClinVar: May 26, 2024 Last updated: Jun 17, 2024 |
Comment:
The stop gained c.5503C>T p.Arg1835Ter variant in BRCA1 has been reported has been reported previously in heterozygous state in patients with breast cancer and ovarian … (more)
The stop gained c.5503C>T p.Arg1835Ter variant in BRCA1 has been reported has been reported previously in heterozygous state in patients with breast cancer and ovarian cancer Hasmad HN et al. 2016. The experimental studies have shown that this premature translational stop signal affects BRCA1 function Ye Q et al 2001. The p.Arg1835Ter variant has allele frequency 0.001% in gnomAD Exomes and is novel not in any individuals in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic multiple submiters. The nucleotide change c.5503C>T in BRCA1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Neoplasm (present)
|
|
Pathogenic
(May 01, 2012)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000109430.4
First in ClinVar: Dec 23, 2013 Last updated: Sep 27, 2014 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001905715.1 First in ClinVar: Sep 23, 2021 Last updated: Sep 23, 2021 |
|
|
Pathogenic
(May 29, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145551.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 40
Observation 2:
Number of individuals with the variant: 3
Geographic origin: Netherlands
Observation 3:
Number of individuals with the variant: 7
Geographic origin: Germany
Observation 4:
Number of individuals with the variant: 2
Geographic origin: Western European
Observation 5:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi
Observation 6:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Germany
Observation 7:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian Non Hispanic
Observation 8:
Number of individuals with the variant: 1
Ethnicity/Population group: German
Geographic origin: Germany
Observation 9:
Number of individuals with the variant: 1
Ethnicity/Population group: Philippine
Observation 10:
Number of individuals with the variant: 21
Ethnicity/Population group: Western European
Observation 11:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Central Eastern European
Observation 12:
Number of individuals with the variant: 1
Ethnicity/Population group: Western Europeanan, Central/Eastern European
|
|
Pathogenic
(Mar 20, 2015)
|
no assertion criteria provided
Method: research
|
Breast-ovarian cancer, familial, 1
Affected status: no
Allele origin:
germline
|
Division of Human Genetics, Children's Hospital of Philadelphia
Study: CSER-PediSeq
Accession: SCV000238467.1 First in ClinVar: Jul 05, 2015 Last updated: Jul 05, 2015 |
Comment:
The heterozygous variant in the BRCA1 gene (c.5503C>T; p.Arg1835*)is considered pathogenic. This change results in a premature stop codon interrupting an important functional domain BRCT2 … (more)
The heterozygous variant in the BRCA1 gene (c.5503C>T; p.Arg1835*)is considered pathogenic. This change results in a premature stop codon interrupting an important functional domain BRCT2 (PMID: 11739404) and premature truncation results in impaired function. This variant has been previously published in 2 individuals of Punjabi ethnicity and part of a cohort of unrelated Pakistani individuals with breast and ovarian cancer (PMID: 16998791), though the paper has no additional information on the phenotype of the affected individuals. This variant has also been seen in multiple affected individuals by other clinical labs (SCV000109430, SCV000145551, SCV000186917, SCV000210227, SCV000077033). (less)
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733584.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
Pathogenic
(Jul 14, 2012)
|
no assertion criteria provided
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000863583.1 First in ClinVar: Dec 24, 2018 Last updated: Dec 24, 2018 |
|
|
Pathogenic
(Dec 01, 2018)
|
no assertion criteria provided
Method: research
|
Ovarian neoplasm
Affected status: yes
Allele origin:
germline
|
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV000923781.1
First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591636.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Arg1835X variant is reported in the literature in 12/7062 proband chromosomes of individuals with breast and ovarian cancer (Bellacosa 2010, Borg 2010, Dizin 2006, … (more)
The p.Arg1835X variant is reported in the literature in 12/7062 proband chromosomes of individuals with breast and ovarian cancer (Bellacosa 2010, Borg 2010, Dizin 2006, Evans 2003, Ferla 2007, Frank 1998, Magnard 2002, Ramus 2007, Rashid 2006, Spurdle 2008); it was not found in any of the 484 control chromosomes. It is listed in dbSNP database as coming from a "clinical source" (ID#: rs#:41293465) but no frequency information was provided, and is therefore, not very informative for assessing the population frequency. The alteration leads to a premature stop codon at position 1835 which is predicted to lead to a truncated or absent protein and loss of function, which is an established disease mechanism for the BRCA1 gene in hereditary breast and ovarian cancer. The variant is reported in the BIC database (x66) and UMD database (x20) as a variant of clinical significance. In addition, two functional studies using the yeast two-hybrid screen and glutathione-S-transferase (GST) pull-down assay, determined that the variant abolished interaction of BRCA1 with two proteins: Acetyl Coenzyme A (CoA) Carboxylase and PABP (Dizin 2006, Magnard 2002). In summary, based on the above information, this variant is classified as pathogenic. (less)
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Pathogenic
(Mar 19, 2021)
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no assertion criteria provided
Method: clinical testing
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Familial cancer of breast
Ovarian cancer Lung cancer
Affected status: no
Allele origin:
somatic
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University Health Network, Princess Margaret Cancer Centre
Accession: SCV001738497.1
First in ClinVar: Jun 26, 2021 Last updated: Jun 26, 2021 |
Secondary finding: yes
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Pathogenic
(Jul 01, 2021)
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no assertion criteria provided
Method: research
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Gastric cancer
Affected status: unknown
Allele origin:
germline
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Laboratory for Genotyping Development, RIKEN
Accession: SCV002758501.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
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Pathogenic
(Jan 31, 2014)
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no assertion criteria provided
Method: research
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587514.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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Pathogenic
(Aug 08, 2021)
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no assertion criteria provided
Method: clinical testing
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Breast carcinoma
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences
Accession: SCV001774816.1
First in ClinVar: Aug 13, 2021 Last updated: Aug 13, 2021 |
Indication for testing: breast cancer
Age: 30-39 years
Sex: female
Comment on evidence:
Invasive Carcinoma EST receptor + PRO receptor - HER2 receptor -
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001955746.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(Feb 20, 2023)
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no assertion criteria provided
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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Cancer Genomics Lab, PINUM Cancer Hospital
Accession: SCV004011752.1
First in ClinVar: Jul 16, 2023 Last updated: Jul 16, 2023 |
Age: 40-49 years
Sex: female
Ethnicity/Population group: Pakistani
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Pathogenic
(Mar 02, 2020)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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BRCAlab, Lund University
Accession: SCV004243905.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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not provided
(-)
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no classification provided
Method: in vitro
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Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
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Brotman Baty Institute, University of Washington
Accession: SCV001237592.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-2.29625062856965
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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functionally_abnormal
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001237592.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5503C>T, a NONSENSE variant, produced a function score of -2.3, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5503C>T, a NONSENSE variant, produced a function score of -2.3, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. | Usui Y | The New England journal of medicine | 2023 | PMID: 36988593 |
The spectrum of BRCA1 and BRCA2 pathogenic sequence variants in Middle Eastern, North African, and South European countries. | Laitman Y | Human mutation | 2019 | PMID: 31209999 |
Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
BRCA germline mutations in an unselected nationwide cohort of Chinese patients with ovarian cancer and healthy controls. | Li A | Gynecologic oncology | 2018 | PMID: 30078507 |
Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations. | Singh J | Breast cancer research and treatment | 2018 | PMID: 29470806 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway. | Heramb C | Hereditary cancer in clinical practice | 2018 | PMID: 29339979 |
Thorough in silico and in vitro cDNA analysis of 21 putative BRCA1 and BRCA2 splice variants and a complex tandem duplication in BRCA2 allowing the identification of activated cryptic splice donor sites in BRCA2 exon 11. | Baert A | Human mutation | 2018 | PMID: 29280214 |
Mutational spectrum in breast cancer associated BRCA1 and BRCA2 genes in Colombia. | Briceño-Balcázar I | Colombia medica (Cali, Colombia) | 2017 | PMID: 29021639 |
Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients. | Sun J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 28724667 |
Multiple-gene panel analysis in a case series of 255 women with hereditary breast and ovarian cancer. | Tedaldi G | Oncotarget | 2017 | PMID: 28423363 |
Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study. | Meisel C | Archives of gynecology and obstetrics | 2017 | PMID: 28324225 |
High prevalence and predominance of BRCA1 germline mutations in Pakistani triple-negative breast cancer patients. | Rashid MU | BMC cancer | 2016 | PMID: 27553291 |
Prevalence and Prognostic Role of BRCA1/2 Variants in Unselected Chinese Breast Cancer Patients. | Zhong X | PloS one | 2016 | PMID: 27257965 |
Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. | Maxwell KN | American journal of human genetics | 2016 | PMID: 27153395 |
Evaluation of germline BRCA1 and BRCA2 mutations in a multi-ethnic Asian cohort of ovarian cancer patients. | Hasmad HN | Gynecologic oncology | 2016 | PMID: 26541979 |
Comprehensive spectrum of BRCA1 and BRCA2 deleterious mutations in breast cancer in Asian countries. | Kwong A | Journal of medical genetics | 2016 | PMID: 26187060 |
Breast and ovarian cancer predisposition due to de novo BRCA1 and BRCA2 mutations. | Golmard L | Oncogene | 2016 | PMID: 26028024 |
Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer. | Wong-Brown MW | Breast cancer research and treatment | 2015 | PMID: 25682074 |
Prevalence and differentiation of hereditary breast and ovarian cancers in Japan. | Nakamura S | Breast cancer (Tokyo, Japan) | 2015 | PMID: 24249303 |
Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes. | Pruss D | Breast cancer research and treatment | 2014 | PMID: 25085752 |
Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes. | Castéra L | European journal of human genetics : EJHG | 2014 | PMID: 24549055 |
Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. | Cunningham JM | Scientific reports | 2014 | PMID: 24504028 |
Classifications within molecular subtypes enables identification of BRCA1/BRCA2 mutation carriers by RNA tumor profiling. | Larsen MJ | PloS one | 2013 | PMID: 23704984 |
Assessment of human Nter and Cter BRCA1 mutations using growth and localization assays in yeast. | Millot GA | Human mutation | 2011 | PMID: 21922593 |
Non-founder BRCA1 mutations in Russian breast cancer patients. | Iyevleva AG | Cancer letters | 2010 | PMID: 20727672 |
Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
Efficiency of BRCAPRO and Myriad II mutation probability thresholds versus cancer history criteria alone for BRCA1/2 mutation detection. | van Harssel JJ | Familial cancer | 2010 | PMID: 19949876 |
BRCA1 and BRCA2 mutations in Danish families with hereditary breast and/or ovarian cancer. | Thomassen M | Acta oncologica (Stockholm, Sweden) | 2008 | PMID: 18465347 |
Histopathological features of 'BRCAX' familial breast cancers in the kConFab resource. | Loughrey M | Pathology | 2008 | PMID: 18446624 |
Founder mutations in BRCA1 and BRCA2 genes. | Ferla R | Annals of oncology : official journal of the European Society for Medical Oncology | 2007 | PMID: 17591843 |
Prevalence of BRCA1 and BRCA2 mutations in Pakistani breast and ovarian cancer patients. | Rashid MU | International journal of cancer | 2006 | PMID: 16998791 |
A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting. | van der Hout AH | Human mutation | 2006 | PMID: 16683254 |
BRCA1, BRCA2 and TP53 mutations in very early-onset breast cancer with associated risks to relatives. | Lalloo F | European journal of cancer (Oxford, England : 1990) | 2006 | PMID: 16644204 |
BRCA1 and BRCA2 mutations in breast and ovarian cancer syndrome: reflection on the Creighton University historical series of high risk families. | Sinilnikova OM | Familial cancer | 2006 | PMID: 16528604 |
Average age-specific cumulative risk of breast cancer according to type and site of germline mutations in BRCA1 and BRCA2 estimated from multiple-case breast cancer families attending Australian family cancer clinics. | Scott CL | Human genetics | 2003 | PMID: 12601471 |
Direct interaction between BRCA1 and the estrogen receptor regulates vascular endothelial growth factor (VEGF) transcription and secretion in breast cancer cells. | Kawai H | Oncogene | 2002 | PMID: 12400015 |
The nonsense-mediated mRNA decay pathway triggers degradation of most BRCA1 mRNAs bearing premature termination codons. | Perrin-Vidoz L | Human molecular genetics | 2002 | PMID: 12393792 |
BRCA1 interacts with acetyl-CoA carboxylase through its tandem of BRCT domains. | Magnard C | Oncogene | 2002 | PMID: 12360400 |
BRCA1 and BRCA2 mutations among breast cancer patients from the Philippines. | De Leon Matsuda ML | International journal of cancer | 2002 | PMID: 11920621 |
Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population. | Meindl A | International journal of cancer | 2002 | PMID: 11802209 |
BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations. | Ye Q | The Journal of cell biology | 2001 | PMID: 11739404 |
Identification of a recurrent BRCA1 mutation in German breast-cancer and/or ovarian-cancer families. | Hofmann W | Journal of cancer research and clinical oncology | 2001 | PMID: 11260866 |
Mutation analysis of BRCA1 and BRCA2 in Turkish cancer families: a novel mutation BRCA2 3414del4 found in male breast cancer. | Balci A | European journal of cancer (Oxford, England : 1990) | 1999 | PMID: 10505028 |
The contribution of germline BRCA1 and BRCA2 mutations to familial ovarian cancer: no evidence for other ovarian cancer-susceptibility genes. | Gayther SA | American journal of human genetics | 1999 | PMID: 10486320 |
A high proportion of mutations in the BRCA1 gene in German breast/ovarian cancer families with clustering of mutations in the 3' third of the gene. | Dong J | Human genetics | 1998 | PMID: 9760198 |
A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families. | Serova O | American journal of human genetics | 1996 | PMID: 8554067 |
https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
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Text-mined citations for rs41293465 ...
HelpRecord last updated Oct 13, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.