Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5109T>G (p.Tyr1703Ter)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Sep 2016 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5109T>G (p.Tyr1703Ter)
Variation ID: 55403 Accession: VCV000055403.35
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43063917 (GRCh38) [ NCBI UCSC ] 17: 41215934 (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 Sep 16, 2024 Sep 8, 2016 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5109T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Tyr1703Ter nonsense NM_001407571.1:c.4896T>G NP_001394500.1:p.Tyr1632Ter nonsense NM_001407581.1:c.5175T>G NP_001394510.1:p.Tyr1725Ter nonsense NM_001407582.1:c.5175T>G NP_001394511.1:p.Tyr1725Ter nonsense NM_001407583.1:c.5172T>G NP_001394512.1:p.Tyr1724Ter nonsense NM_001407585.1:c.5172T>G NP_001394514.1:p.Tyr1724Ter nonsense NM_001407587.1:c.5172T>G NP_001394516.1:p.Tyr1724Ter nonsense NM_001407590.1:c.5169T>G NP_001394519.1:p.Tyr1723Ter nonsense NM_001407591.1:c.5169T>G NP_001394520.1:p.Tyr1723Ter nonsense NM_001407593.1:c.5109T>G NP_001394522.1:p.Tyr1703Ter nonsense NM_001407594.1:c.5109T>G NP_001394523.1:p.Tyr1703Ter nonsense NM_001407596.1:c.5109T>G NP_001394525.1:p.Tyr1703Ter nonsense NM_001407597.1:c.5109T>G NP_001394526.1:p.Tyr1703Ter nonsense NM_001407598.1:c.5109T>G NP_001394527.1:p.Tyr1703Ter nonsense NM_001407602.1:c.5109T>G NP_001394531.1:p.Tyr1703Ter nonsense NM_001407603.1:c.5109T>G NP_001394532.1:p.Tyr1703Ter nonsense NM_001407605.1:c.5109T>G NP_001394534.1:p.Tyr1703Ter nonsense NM_001407610.1:c.5106T>G NP_001394539.1:p.Tyr1702Ter nonsense NM_001407611.1:c.5106T>G NP_001394540.1:p.Tyr1702Ter nonsense NM_001407612.1:c.5106T>G NP_001394541.1:p.Tyr1702Ter nonsense NM_001407613.1:c.5106T>G NP_001394542.1:p.Tyr1702Ter nonsense NM_001407614.1:c.5106T>G NP_001394543.1:p.Tyr1702Ter nonsense NM_001407615.1:c.5106T>G NP_001394544.1:p.Tyr1702Ter nonsense NM_001407616.1:c.5106T>G NP_001394545.1:p.Tyr1702Ter nonsense NM_001407617.1:c.5106T>G NP_001394546.1:p.Tyr1702Ter nonsense NM_001407618.1:c.5106T>G NP_001394547.1:p.Tyr1702Ter nonsense NM_001407619.1:c.5106T>G NP_001394548.1:p.Tyr1702Ter nonsense NM_001407620.1:c.5106T>G NP_001394549.1:p.Tyr1702Ter nonsense NM_001407621.1:c.5106T>G NP_001394550.1:p.Tyr1702Ter nonsense NM_001407622.1:c.5106T>G NP_001394551.1:p.Tyr1702Ter nonsense NM_001407623.1:c.5106T>G NP_001394552.1:p.Tyr1702Ter nonsense NM_001407624.1:c.5106T>G NP_001394553.1:p.Tyr1702Ter nonsense NM_001407625.1:c.5106T>G NP_001394554.1:p.Tyr1702Ter nonsense NM_001407626.1:c.5106T>G NP_001394555.1:p.Tyr1702Ter nonsense NM_001407627.1:c.5103T>G NP_001394556.1:p.Tyr1701Ter nonsense NM_001407628.1:c.5103T>G NP_001394557.1:p.Tyr1701Ter nonsense NM_001407629.1:c.5103T>G NP_001394558.1:p.Tyr1701Ter nonsense NM_001407630.1:c.5103T>G NP_001394559.1:p.Tyr1701Ter nonsense NM_001407631.1:c.5103T>G NP_001394560.1:p.Tyr1701Ter nonsense NM_001407632.1:c.5103T>G NP_001394561.1:p.Tyr1701Ter nonsense NM_001407633.1:c.5103T>G NP_001394562.1:p.Tyr1701Ter nonsense NM_001407634.1:c.5103T>G NP_001394563.1:p.Tyr1701Ter nonsense NM_001407635.1:c.5103T>G NP_001394564.1:p.Tyr1701Ter nonsense NM_001407636.1:c.5103T>G NP_001394565.1:p.Tyr1701Ter nonsense NM_001407637.1:c.5103T>G NP_001394566.1:p.Tyr1701Ter nonsense NM_001407638.1:c.5103T>G NP_001394567.1:p.Tyr1701Ter nonsense NM_001407639.1:c.5103T>G NP_001394568.1:p.Tyr1701Ter nonsense NM_001407640.1:c.5103T>G NP_001394569.1:p.Tyr1701Ter nonsense NM_001407641.1:c.5103T>G NP_001394570.1:p.Tyr1701Ter nonsense NM_001407642.1:c.5103T>G NP_001394571.1:p.Tyr1701Ter nonsense NM_001407644.1:c.5100T>G NP_001394573.1:p.Tyr1700Ter nonsense NM_001407645.1:c.5100T>G NP_001394574.1:p.Tyr1700Ter nonsense NM_001407646.1:c.5097T>G NP_001394575.1:p.Tyr1699Ter nonsense NM_001407647.1:c.5094T>G NP_001394576.1:p.Tyr1698Ter nonsense NM_001407648.1:c.5052T>G NP_001394577.1:p.Tyr1684Ter nonsense NM_001407649.1:c.5049T>G NP_001394578.1:p.Tyr1683Ter nonsense NM_001407653.1:c.5031T>G NP_001394582.1:p.Tyr1677Ter nonsense NM_001407654.1:c.5031T>G NP_001394583.1:p.Tyr1677Ter nonsense NM_001407655.1:c.5031T>G NP_001394584.1:p.Tyr1677Ter nonsense NM_001407656.1:c.5028T>G NP_001394585.1:p.Tyr1676Ter nonsense NM_001407657.1:c.5028T>G NP_001394586.1:p.Tyr1676Ter nonsense NM_001407658.1:c.5028T>G NP_001394587.1:p.Tyr1676Ter nonsense NM_001407659.1:c.5025T>G NP_001394588.1:p.Tyr1675Ter nonsense NM_001407660.1:c.5025T>G NP_001394589.1:p.Tyr1675Ter nonsense NM_001407661.1:c.5025T>G NP_001394590.1:p.Tyr1675Ter nonsense NM_001407662.1:c.5025T>G NP_001394591.1:p.Tyr1675Ter nonsense NM_001407663.1:c.5025T>G NP_001394592.1:p.Tyr1675Ter nonsense NM_001407664.1:c.4986T>G NP_001394593.1:p.Tyr1662Ter nonsense NM_001407665.1:c.4986T>G NP_001394594.1:p.Tyr1662Ter nonsense NM_001407666.1:c.4986T>G NP_001394595.1:p.Tyr1662Ter nonsense NM_001407667.1:c.4986T>G NP_001394596.1:p.Tyr1662Ter nonsense NM_001407668.1:c.4986T>G NP_001394597.1:p.Tyr1662Ter nonsense NM_001407669.1:c.4986T>G NP_001394598.1:p.Tyr1662Ter nonsense NM_001407670.1:c.4983T>G NP_001394599.1:p.Tyr1661Ter nonsense NM_001407671.1:c.4983T>G NP_001394600.1:p.Tyr1661Ter nonsense NM_001407672.1:c.4983T>G NP_001394601.1:p.Tyr1661Ter nonsense NM_001407673.1:c.4983T>G NP_001394602.1:p.Tyr1661Ter nonsense NM_001407674.1:c.4983T>G NP_001394603.1:p.Tyr1661Ter nonsense NM_001407675.1:c.4983T>G NP_001394604.1:p.Tyr1661Ter nonsense NM_001407676.1:c.4983T>G NP_001394605.1:p.Tyr1661Ter nonsense NM_001407677.1:c.4983T>G NP_001394606.1:p.Tyr1661Ter nonsense NM_001407678.1:c.4983T>G NP_001394607.1:p.Tyr1661Ter nonsense NM_001407679.1:c.4983T>G NP_001394608.1:p.Tyr1661Ter nonsense NM_001407680.1:c.4983T>G NP_001394609.1:p.Tyr1661Ter nonsense NM_001407681.1:c.4980T>G NP_001394610.1:p.Tyr1660Ter nonsense NM_001407682.1:c.4980T>G NP_001394611.1:p.Tyr1660Ter nonsense NM_001407683.1:c.4980T>G NP_001394612.1:p.Tyr1660Ter nonsense NM_001407684.1:c.5109T>G NP_001394613.1:p.Tyr1703Ter nonsense NM_001407685.1:c.4980T>G NP_001394614.1:p.Tyr1660Ter nonsense NM_001407686.1:c.4980T>G NP_001394615.1:p.Tyr1660Ter nonsense NM_001407687.1:c.4980T>G NP_001394616.1:p.Tyr1660Ter nonsense NM_001407688.1:c.4980T>G NP_001394617.1:p.Tyr1660Ter nonsense NM_001407689.1:c.4980T>G NP_001394618.1:p.Tyr1660Ter nonsense NM_001407690.1:c.4977T>G NP_001394619.1:p.Tyr1659Ter nonsense NM_001407691.1:c.4977T>G NP_001394620.1:p.Tyr1659Ter nonsense NM_001407692.1:c.4968T>G NP_001394621.1:p.Tyr1656Ter nonsense NM_001407694.1:c.4968T>G NP_001394623.1:p.Tyr1656Ter nonsense NM_001407695.1:c.4968T>G NP_001394624.1:p.Tyr1656Ter nonsense NM_001407696.1:c.4968T>G NP_001394625.1:p.Tyr1656Ter nonsense NM_001407697.1:c.4968T>G NP_001394626.1:p.Tyr1656Ter nonsense NM_001407698.1:c.4968T>G NP_001394627.1:p.Tyr1656Ter nonsense NM_001407724.1:c.4968T>G NP_001394653.1:p.Tyr1656Ter nonsense NM_001407725.1:c.4968T>G NP_001394654.1:p.Tyr1656Ter nonsense NM_001407726.1:c.4968T>G NP_001394655.1:p.Tyr1656Ter nonsense NM_001407727.1:c.4968T>G NP_001394656.1:p.Tyr1656Ter nonsense NM_001407728.1:c.4968T>G NP_001394657.1:p.Tyr1656Ter nonsense NM_001407729.1:c.4968T>G NP_001394658.1:p.Tyr1656Ter nonsense NM_001407730.1:c.4968T>G NP_001394659.1:p.Tyr1656Ter nonsense NM_001407731.1:c.4968T>G NP_001394660.1:p.Tyr1656Ter nonsense NM_001407732.1:c.4965T>G NP_001394661.1:p.Tyr1655Ter nonsense NM_001407733.1:c.4965T>G NP_001394662.1:p.Tyr1655Ter nonsense NM_001407734.1:c.4965T>G NP_001394663.1:p.Tyr1655Ter nonsense NM_001407735.1:c.4965T>G NP_001394664.1:p.Tyr1655Ter nonsense NM_001407736.1:c.4965T>G NP_001394665.1:p.Tyr1655Ter nonsense NM_001407737.1:c.4965T>G NP_001394666.1:p.Tyr1655Ter nonsense NM_001407738.1:c.4965T>G NP_001394667.1:p.Tyr1655Ter nonsense NM_001407739.1:c.4965T>G NP_001394668.1:p.Tyr1655Ter nonsense NM_001407740.1:c.4965T>G NP_001394669.1:p.Tyr1655Ter nonsense NM_001407741.1:c.4965T>G NP_001394670.1:p.Tyr1655Ter nonsense NM_001407742.1:c.4965T>G NP_001394671.1:p.Tyr1655Ter nonsense NM_001407743.1:c.4965T>G NP_001394672.1:p.Tyr1655Ter nonsense NM_001407744.1:c.4965T>G NP_001394673.1:p.Tyr1655Ter nonsense NM_001407745.1:c.4965T>G NP_001394674.1:p.Tyr1655Ter nonsense NM_001407746.1:c.4965T>G NP_001394675.1:p.Tyr1655Ter nonsense NM_001407747.1:c.4965T>G NP_001394676.1:p.Tyr1655Ter nonsense NM_001407748.1:c.4965T>G NP_001394677.1:p.Tyr1655Ter nonsense NM_001407749.1:c.4965T>G NP_001394678.1:p.Tyr1655Ter nonsense NM_001407750.1:c.4965T>G NP_001394679.1:p.Tyr1655Ter nonsense NM_001407751.1:c.4965T>G NP_001394680.1:p.Tyr1655Ter nonsense NM_001407752.1:c.4965T>G NP_001394681.1:p.Tyr1655Ter nonsense NM_001407838.1:c.4962T>G NP_001394767.1:p.Tyr1654Ter nonsense NM_001407839.1:c.4962T>G NP_001394768.1:p.Tyr1654Ter nonsense NM_001407841.1:c.4962T>G NP_001394770.1:p.Tyr1654Ter nonsense NM_001407842.1:c.4962T>G NP_001394771.1:p.Tyr1654Ter nonsense NM_001407843.1:c.4962T>G NP_001394772.1:p.Tyr1654Ter nonsense NM_001407844.1:c.4962T>G NP_001394773.1:p.Tyr1654Ter nonsense NM_001407845.1:c.4962T>G NP_001394774.1:p.Tyr1654Ter nonsense NM_001407846.1:c.4962T>G NP_001394775.1:p.Tyr1654Ter nonsense NM_001407847.1:c.4962T>G NP_001394776.1:p.Tyr1654Ter nonsense NM_001407848.1:c.4962T>G NP_001394777.1:p.Tyr1654Ter nonsense NM_001407849.1:c.4962T>G NP_001394778.1:p.Tyr1654Ter nonsense NM_001407850.1:c.4962T>G NP_001394779.1:p.Tyr1654Ter nonsense NM_001407851.1:c.4962T>G NP_001394780.1:p.Tyr1654Ter nonsense NM_001407852.1:c.4962T>G NP_001394781.1:p.Tyr1654Ter nonsense NM_001407853.1:c.4962T>G NP_001394782.1:p.Tyr1654Ter nonsense NM_001407854.1:c.5109T>G NP_001394783.1:p.Tyr1703Ter nonsense NM_001407858.1:c.5106T>G NP_001394787.1:p.Tyr1702Ter nonsense NM_001407859.1:c.5106T>G NP_001394788.1:p.Tyr1702Ter nonsense NM_001407860.1:c.5106T>G NP_001394789.1:p.Tyr1702Ter nonsense NM_001407861.1:c.5103T>G NP_001394790.1:p.Tyr1701Ter nonsense NM_001407862.1:c.4908T>G NP_001394791.1:p.Tyr1636Ter nonsense NM_001407874.1:c.4902T>G NP_001394803.1:p.Tyr1634Ter nonsense NM_001407875.1:c.4902T>G NP_001394804.1:p.Tyr1634Ter nonsense NM_001407879.1:c.4899T>G NP_001394808.1:p.Tyr1633Ter nonsense NM_001407881.1:c.4899T>G NP_001394810.1:p.Tyr1633Ter nonsense NM_001407882.1:c.4899T>G NP_001394811.1:p.Tyr1633Ter nonsense NM_001407884.1:c.4899T>G NP_001394813.1:p.Tyr1633Ter nonsense NM_001407885.1:c.4899T>G NP_001394814.1:p.Tyr1633Ter nonsense NM_001407886.1:c.4899T>G NP_001394815.1:p.Tyr1633Ter nonsense NM_001407887.1:c.4899T>G NP_001394816.1:p.Tyr1633Ter nonsense NM_001407889.1:c.4899T>G NP_001394818.1:p.Tyr1633Ter nonsense NM_001407894.1:c.4896T>G NP_001394823.1:p.Tyr1632Ter nonsense NM_001407895.1:c.4896T>G NP_001394824.1:p.Tyr1632Ter nonsense NM_001407896.1:c.4896T>G NP_001394825.1:p.Tyr1632Ter nonsense NM_001407897.1:c.4896T>G NP_001394826.1:p.Tyr1632Ter nonsense NM_001407898.1:c.4896T>G NP_001394827.1:p.Tyr1632Ter nonsense NM_001407899.1:c.4896T>G NP_001394828.1:p.Tyr1632Ter nonsense NM_001407900.1:c.4896T>G NP_001394829.1:p.Tyr1632Ter nonsense NM_001407902.1:c.4896T>G NP_001394831.1:p.Tyr1632Ter nonsense NM_001407904.1:c.4896T>G NP_001394833.1:p.Tyr1632Ter nonsense NM_001407906.1:c.4896T>G NP_001394835.1:p.Tyr1632Ter nonsense NM_001407907.1:c.4896T>G NP_001394836.1:p.Tyr1632Ter nonsense NM_001407908.1:c.4896T>G NP_001394837.1:p.Tyr1632Ter nonsense NM_001407909.1:c.4896T>G NP_001394838.1:p.Tyr1632Ter nonsense NM_001407910.1:c.4896T>G NP_001394839.1:p.Tyr1632Ter nonsense NM_001407915.1:c.4893T>G NP_001394844.1:p.Tyr1631Ter nonsense NM_001407916.1:c.4893T>G NP_001394845.1:p.Tyr1631Ter nonsense NM_001407917.1:c.4893T>G NP_001394846.1:p.Tyr1631Ter nonsense NM_001407918.1:c.4893T>G NP_001394847.1:p.Tyr1631Ter nonsense NM_001407919.1:c.4986T>G NP_001394848.1:p.Tyr1662Ter nonsense NM_001407920.1:c.4845T>G NP_001394849.1:p.Tyr1615Ter nonsense NM_001407921.1:c.4845T>G NP_001394850.1:p.Tyr1615Ter nonsense NM_001407922.1:c.4845T>G NP_001394851.1:p.Tyr1615Ter nonsense NM_001407923.1:c.4845T>G NP_001394852.1:p.Tyr1615Ter nonsense NM_001407924.1:c.4845T>G NP_001394853.1:p.Tyr1615Ter nonsense NM_001407925.1:c.4845T>G NP_001394854.1:p.Tyr1615Ter nonsense NM_001407926.1:c.4845T>G NP_001394855.1:p.Tyr1615Ter nonsense NM_001407927.1:c.4842T>G NP_001394856.1:p.Tyr1614Ter nonsense NM_001407928.1:c.4842T>G NP_001394857.1:p.Tyr1614Ter nonsense NM_001407929.1:c.4842T>G NP_001394858.1:p.Tyr1614Ter nonsense NM_001407930.1:c.4842T>G NP_001394859.1:p.Tyr1614Ter nonsense NM_001407931.1:c.4842T>G NP_001394860.1:p.Tyr1614Ter nonsense NM_001407932.1:c.4842T>G NP_001394861.1:p.Tyr1614Ter nonsense NM_001407933.1:c.4842T>G NP_001394862.1:p.Tyr1614Ter nonsense NM_001407934.1:c.4839T>G NP_001394863.1:p.Tyr1613Ter nonsense NM_001407935.1:c.4839T>G NP_001394864.1:p.Tyr1613Ter nonsense NM_001407936.1:c.4839T>G NP_001394865.1:p.Tyr1613Ter nonsense NM_001407937.1:c.4986T>G NP_001394866.1:p.Tyr1662Ter nonsense NM_001407938.1:c.4986T>G NP_001394867.1:p.Tyr1662Ter nonsense NM_001407939.1:c.4983T>G NP_001394868.1:p.Tyr1661Ter nonsense NM_001407940.1:c.4983T>G NP_001394869.1:p.Tyr1661Ter nonsense NM_001407941.1:c.4980T>G NP_001394870.1:p.Tyr1660Ter nonsense NM_001407942.1:c.4968T>G NP_001394871.1:p.Tyr1656Ter nonsense NM_001407943.1:c.4965T>G NP_001394872.1:p.Tyr1655Ter nonsense NM_001407944.1:c.4965T>G NP_001394873.1:p.Tyr1655Ter nonsense NM_001407945.1:c.4965T>G NP_001394874.1:p.Tyr1655Ter nonsense NM_001407946.1:c.4776T>G NP_001394875.1:p.Tyr1592Ter nonsense NM_001407947.1:c.4776T>G NP_001394876.1:p.Tyr1592Ter nonsense NM_001407948.1:c.4776T>G NP_001394877.1:p.Tyr1592Ter nonsense NM_001407949.1:c.4776T>G NP_001394878.1:p.Tyr1592Ter nonsense NM_001407950.1:c.4773T>G NP_001394879.1:p.Tyr1591Ter nonsense NM_001407951.1:c.4773T>G NP_001394880.1:p.Tyr1591Ter nonsense NM_001407952.1:c.4773T>G NP_001394881.1:p.Tyr1591Ter nonsense NM_001407953.1:c.4773T>G NP_001394882.1:p.Tyr1591Ter nonsense NM_001407954.1:c.4773T>G NP_001394883.1:p.Tyr1591Ter nonsense NM_001407955.1:c.4773T>G NP_001394884.1:p.Tyr1591Ter nonsense NM_001407956.1:c.4770T>G NP_001394885.1:p.Tyr1590Ter nonsense NM_001407957.1:c.4770T>G NP_001394886.1:p.Tyr1590Ter nonsense NM_001407958.1:c.4770T>G NP_001394887.1:p.Tyr1590Ter nonsense NM_001407959.1:c.4728T>G NP_001394888.1:p.Tyr1576Ter nonsense NM_001407960.1:c.4725T>G NP_001394889.1:p.Tyr1575Ter nonsense NM_001407962.1:c.4725T>G NP_001394891.1:p.Tyr1575Ter nonsense NM_001407963.1:c.4722T>G NP_001394892.1:p.Tyr1574Ter nonsense NM_001407964.1:c.4647T>G NP_001394893.1:p.Tyr1549Ter nonsense NM_001407965.1:c.4602T>G NP_001394894.1:p.Tyr1534Ter nonsense NM_001407966.1:c.4221T>G NP_001394895.1:p.Tyr1407Ter nonsense NM_001407967.1:c.4218T>G NP_001394896.1:p.Tyr1406Ter nonsense NM_001407968.1:c.2505T>G NP_001394897.1:p.Tyr835Ter nonsense NM_001407969.1:c.2502T>G NP_001394898.1:p.Tyr834Ter nonsense NM_001407970.1:c.1866T>G NP_001394899.1:p.Tyr622Ter nonsense NM_001407971.1:c.1866T>G NP_001394900.1:p.Tyr622Ter nonsense NM_001407972.1:c.1863T>G NP_001394901.1:p.Tyr621Ter nonsense NM_001407973.1:c.1800T>G NP_001394902.1:p.Tyr600Ter nonsense NM_001407974.1:c.1800T>G NP_001394903.1:p.Tyr600Ter nonsense NM_001407975.1:c.1800T>G NP_001394904.1:p.Tyr600Ter nonsense NM_001407976.1:c.1800T>G NP_001394905.1:p.Tyr600Ter nonsense NM_001407977.1:c.1800T>G NP_001394906.1:p.Tyr600Ter nonsense NM_001407978.1:c.1800T>G NP_001394907.1:p.Tyr600Ter nonsense NM_001407979.1:c.1797T>G NP_001394908.1:p.Tyr599Ter nonsense NM_001407980.1:c.1797T>G NP_001394909.1:p.Tyr599Ter nonsense NM_001407981.1:c.1797T>G NP_001394910.1:p.Tyr599Ter nonsense NM_001407982.1:c.1797T>G NP_001394911.1:p.Tyr599Ter nonsense NM_001407983.1:c.1797T>G NP_001394912.1:p.Tyr599Ter nonsense NM_001407984.1:c.1797T>G NP_001394913.1:p.Tyr599Ter nonsense NM_001407985.1:c.1797T>G NP_001394914.1:p.Tyr599Ter nonsense NM_001407986.1:c.1797T>G NP_001394915.1:p.Tyr599Ter nonsense NM_001407990.1:c.1797T>G NP_001394919.1:p.Tyr599Ter nonsense NM_001407991.1:c.1797T>G NP_001394920.1:p.Tyr599Ter nonsense NM_001407992.1:c.1797T>G NP_001394921.1:p.Tyr599Ter nonsense NM_001407993.1:c.1797T>G NP_001394922.1:p.Tyr599Ter nonsense NM_001408392.1:c.1794T>G NP_001395321.1:p.Tyr598Ter nonsense NM_001408396.1:c.1794T>G NP_001395325.1:p.Tyr598Ter nonsense NM_001408397.1:c.1794T>G NP_001395326.1:p.Tyr598Ter nonsense NM_001408398.1:c.1794T>G NP_001395327.1:p.Tyr598Ter nonsense NM_001408399.1:c.1794T>G NP_001395328.1:p.Tyr598Ter nonsense NM_001408400.1:c.1794T>G NP_001395329.1:p.Tyr598Ter nonsense NM_001408401.1:c.1794T>G NP_001395330.1:p.Tyr598Ter nonsense NM_001408402.1:c.1794T>G NP_001395331.1:p.Tyr598Ter nonsense NM_001408403.1:c.1794T>G NP_001395332.1:p.Tyr598Ter nonsense NM_001408404.1:c.1794T>G NP_001395333.1:p.Tyr598Ter nonsense NM_001408406.1:c.1791T>G NP_001395335.1:p.Tyr597Ter nonsense NM_001408407.1:c.1791T>G NP_001395336.1:p.Tyr597Ter nonsense NM_001408408.1:c.1791T>G NP_001395337.1:p.Tyr597Ter nonsense NM_001408409.1:c.1788T>G NP_001395338.1:p.Tyr596Ter nonsense NM_001408410.1:c.1725T>G NP_001395339.1:p.Tyr575Ter nonsense NM_001408411.1:c.1722T>G NP_001395340.1:p.Tyr574Ter nonsense NM_001408412.1:c.1719T>G NP_001395341.1:p.Tyr573Ter nonsense NM_001408413.1:c.1719T>G NP_001395342.1:p.Tyr573Ter nonsense NM_001408414.1:c.1719T>G NP_001395343.1:p.Tyr573Ter nonsense NM_001408415.1:c.1719T>G NP_001395344.1:p.Tyr573Ter nonsense NM_001408416.1:c.1719T>G NP_001395345.1:p.Tyr573Ter nonsense NM_001408418.1:c.1683T>G NP_001395347.1:p.Tyr561Ter nonsense NM_001408419.1:c.1683T>G NP_001395348.1:p.Tyr561Ter nonsense NM_001408420.1:c.1683T>G NP_001395349.1:p.Tyr561Ter nonsense NM_001408421.1:c.1680T>G NP_001395350.1:p.Tyr560Ter nonsense NM_001408422.1:c.1680T>G NP_001395351.1:p.Tyr560Ter nonsense NM_001408423.1:c.1680T>G NP_001395352.1:p.Tyr560Ter nonsense NM_001408424.1:c.1680T>G NP_001395353.1:p.Tyr560Ter nonsense NM_001408425.1:c.1677T>G NP_001395354.1:p.Tyr559Ter nonsense NM_001408426.1:c.1677T>G NP_001395355.1:p.Tyr559Ter nonsense NM_001408427.1:c.1677T>G NP_001395356.1:p.Tyr559Ter nonsense NM_001408428.1:c.1677T>G NP_001395357.1:p.Tyr559Ter nonsense NM_001408429.1:c.1677T>G NP_001395358.1:p.Tyr559Ter nonsense NM_001408430.1:c.1677T>G NP_001395359.1:p.Tyr559Ter nonsense NM_001408431.1:c.1677T>G NP_001395360.1:p.Tyr559Ter nonsense NM_001408432.1:c.1674T>G NP_001395361.1:p.Tyr558Ter nonsense NM_001408433.1:c.1674T>G NP_001395362.1:p.Tyr558Ter nonsense NM_001408434.1:c.1674T>G NP_001395363.1:p.Tyr558Ter nonsense NM_001408435.1:c.1674T>G NP_001395364.1:p.Tyr558Ter nonsense NM_001408436.1:c.1674T>G NP_001395365.1:p.Tyr558Ter nonsense NM_001408437.1:c.1674T>G NP_001395366.1:p.Tyr558Ter nonsense NM_001408438.1:c.1674T>G NP_001395367.1:p.Tyr558Ter nonsense NM_001408439.1:c.1674T>G NP_001395368.1:p.Tyr558Ter nonsense NM_001408440.1:c.1674T>G NP_001395369.1:p.Tyr558Ter nonsense NM_001408441.1:c.1674T>G NP_001395370.1:p.Tyr558Ter nonsense NM_001408442.1:c.1674T>G NP_001395371.1:p.Tyr558Ter nonsense NM_001408443.1:c.1674T>G NP_001395372.1:p.Tyr558Ter nonsense NM_001408444.1:c.1674T>G NP_001395373.1:p.Tyr558Ter nonsense NM_001408445.1:c.1671T>G NP_001395374.1:p.Tyr557Ter nonsense NM_001408446.1:c.1671T>G NP_001395375.1:p.Tyr557Ter nonsense NM_001408447.1:c.1671T>G NP_001395376.1:p.Tyr557Ter nonsense NM_001408448.1:c.1671T>G NP_001395377.1:p.Tyr557Ter nonsense NM_001408450.1:c.1671T>G NP_001395379.1:p.Tyr557Ter nonsense NM_001408451.1:c.1665T>G NP_001395380.1:p.Tyr555Ter nonsense NM_001408452.1:c.1659T>G NP_001395381.1:p.Tyr553Ter nonsense NM_001408453.1:c.1659T>G NP_001395382.1:p.Tyr553Ter nonsense NM_001408454.1:c.1659T>G NP_001395383.1:p.Tyr553Ter nonsense NM_001408455.1:c.1659T>G NP_001395384.1:p.Tyr553Ter nonsense NM_001408456.1:c.1659T>G NP_001395385.1:p.Tyr553Ter nonsense NM_001408457.1:c.1659T>G NP_001395386.1:p.Tyr553Ter nonsense NM_001408458.1:c.1656T>G NP_001395387.1:p.Tyr552Ter nonsense NM_001408459.1:c.1656T>G NP_001395388.1:p.Tyr552Ter nonsense NM_001408460.1:c.1656T>G NP_001395389.1:p.Tyr552Ter nonsense NM_001408461.1:c.1656T>G NP_001395390.1:p.Tyr552Ter nonsense NM_001408462.1:c.1656T>G NP_001395391.1:p.Tyr552Ter nonsense NM_001408463.1:c.1656T>G NP_001395392.1:p.Tyr552Ter nonsense NM_001408464.1:c.1656T>G NP_001395393.1:p.Tyr552Ter nonsense NM_001408465.1:c.1656T>G NP_001395394.1:p.Tyr552Ter nonsense NM_001408466.1:c.1656T>G NP_001395395.1:p.Tyr552Ter nonsense NM_001408467.1:c.1656T>G NP_001395396.1:p.Tyr552Ter nonsense NM_001408468.1:c.1653T>G NP_001395397.1:p.Tyr551Ter nonsense NM_001408469.1:c.1653T>G NP_001395398.1:p.Tyr551Ter nonsense NM_001408470.1:c.1653T>G NP_001395399.1:p.Tyr551Ter nonsense NM_001408472.1:c.1797T>G NP_001395401.1:p.Tyr599Ter nonsense NM_001408473.1:c.1794T>G NP_001395402.1:p.Tyr598Ter nonsense NM_001408474.1:c.1599T>G NP_001395403.1:p.Tyr533Ter nonsense NM_001408475.1:c.1596T>G NP_001395404.1:p.Tyr532Ter nonsense NM_001408476.1:c.1596T>G NP_001395405.1:p.Tyr532Ter nonsense NM_001408478.1:c.1590T>G NP_001395407.1:p.Tyr530Ter nonsense NM_001408479.1:c.1590T>G NP_001395408.1:p.Tyr530Ter nonsense NM_001408480.1:c.1590T>G NP_001395409.1:p.Tyr530Ter nonsense NM_001408481.1:c.1587T>G NP_001395410.1:p.Tyr529Ter nonsense NM_001408482.1:c.1587T>G NP_001395411.1:p.Tyr529Ter nonsense NM_001408483.1:c.1587T>G NP_001395412.1:p.Tyr529Ter nonsense NM_001408484.1:c.1587T>G NP_001395413.1:p.Tyr529Ter nonsense NM_001408485.1:c.1587T>G NP_001395414.1:p.Tyr529Ter nonsense NM_001408489.1:c.1587T>G NP_001395418.1:p.Tyr529Ter nonsense NM_001408490.1:c.1587T>G NP_001395419.1:p.Tyr529Ter nonsense NM_001408491.1:c.1587T>G NP_001395420.1:p.Tyr529Ter nonsense NM_001408492.1:c.1584T>G NP_001395421.1:p.Tyr528Ter nonsense NM_001408493.1:c.1584T>G NP_001395422.1:p.Tyr528Ter nonsense NM_001408494.1:c.1560T>G NP_001395423.1:p.Tyr520Ter nonsense NM_001408495.1:c.1554T>G NP_001395424.1:p.Tyr518Ter nonsense NM_001408496.1:c.1536T>G NP_001395425.1:p.Tyr512Ter nonsense NM_001408497.1:c.1536T>G NP_001395426.1:p.Tyr512Ter nonsense NM_001408498.1:c.1536T>G NP_001395427.1:p.Tyr512Ter nonsense NM_001408499.1:c.1536T>G NP_001395428.1:p.Tyr512Ter nonsense NM_001408500.1:c.1536T>G NP_001395429.1:p.Tyr512Ter nonsense NM_001408501.1:c.1536T>G NP_001395430.1:p.Tyr512Ter nonsense NM_001408502.1:c.1533T>G NP_001395431.1:p.Tyr511Ter nonsense NM_001408503.1:c.1533T>G NP_001395432.1:p.Tyr511Ter nonsense NM_001408504.1:c.1533T>G NP_001395433.1:p.Tyr511Ter nonsense NM_001408505.1:c.1530T>G NP_001395434.1:p.Tyr510Ter nonsense NM_001408506.1:c.1473T>G NP_001395435.1:p.Tyr491Ter nonsense NM_001408507.1:c.1470T>G NP_001395436.1:p.Tyr490Ter nonsense NM_001408508.1:c.1461T>G NP_001395437.1:p.Tyr487Ter nonsense NM_001408509.1:c.1458T>G NP_001395438.1:p.Tyr486Ter nonsense NM_001408510.1:c.1419T>G NP_001395439.1:p.Tyr473Ter nonsense NM_001408511.1:c.1416T>G NP_001395440.1:p.Tyr472Ter nonsense NM_001408512.1:c.1296T>G NP_001395441.1:p.Tyr432Ter nonsense NM_001408513.1:c.1269T>G NP_001395442.1:p.Tyr423Ter nonsense NM_001408514.1:c.873T>G NP_001395443.1:p.Tyr291Ter nonsense NM_007297.4:c.4968T>G NP_009228.2:p.Tyr1656Ter nonsense NM_007298.4:c.1797T>G NP_009229.2:p.Tyr599Ter nonsense NM_007299.4:c.1797T>G NP_009230.2:p.Tyr599Ter nonsense NM_007300.4:c.5172T>G NP_009231.2:p.Tyr1724Ter nonsense NM_007304.2:c.1797T>G NP_009235.2:p.Tyr599Ter nonsense NR_027676.2:n.5286T>G non-coding transcript variant NC_000017.11:g.43063917A>C NC_000017.10:g.41215934A>C NG_005905.2:g.154067T>G LRG_292:g.154067T>G LRG_292t1:c.5109T>G LRG_292p1:p.Tyr1703Ter U14680.1:n.5228T>G - Protein change
- Y1703*, Y599*, Y1656*, Y1724*, Y1576*, Y1613*, Y1614*, Y1615*, Y1633*, Y1655*, Y1659*, Y1661*, Y1662*, Y1677*, Y1684*, Y1701*, Y291*, Y512*, Y520*, Y1406*, Y1574*, Y1575*, Y1654*, Y1675*, Y1683*, Y487*, Y490*, Y511*, Y529*, Y555*, Y561*, Y574*, Y597*, Y598*, Y532*, Y558*, Y560*, Y596*, Y600*, Y834*, Y1549*, Y1591*, Y1632*, Y1634*, Y1636*, Y1660*, Y1676*, Y1700*, Y1725*, Y432*, Y472*, Y473*, Y486*, Y491*, Y510*, Y518*, Y533*, Y557*, Y559*, Y573*, Y575*, Y621*, Y622*, Y835*, Y1407*, Y1534*, Y1590*, Y1592*, Y1631*, Y1698*, Y1699*, Y1702*, Y1723*, Y423*, Y528*, Y530*, Y551*, Y552*, Y553*
- Other names
-
p.Y1703*:TAT>TAG
5228T>G
- Canonical SPDI
- NC_000017.11:43063916:A:C
-
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.5109T>G, a NONSENSE variant, produced a function score of -2.17, 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.
- -
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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 |
13044 | 14850 | |
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 (4) |
criteria provided, multiple submitters, no conflicts
|
Jul 31, 2024 | RCV000048797.27 | |
| Pathogenic (8) |
reviewed by expert panel
|
Sep 8, 2016 | RCV000077597.22 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Dec 5, 2022 | RCV000162883.18 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Dec 1, 2023 | RCV000195365.24 |
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
(Sep 08, 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: SCV000300202.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
Pathogenic
(Mar 10, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV000839888.1
First in ClinVar: Nov 05, 2016 Last updated: Nov 05, 2016 |
Comment:
The c.5109T>G (p.Tyr1703*) variant has been reported in 18 patients in the Breast Cancer Information Core database. This variant was also reported in multiple patients … (more)
The c.5109T>G (p.Tyr1703*) variant has been reported in 18 patients in the Breast Cancer Information Core database. This variant was also reported in multiple patients in ClinVar and classified as a pathogenic variant by an expert panel (https://www.ncbi.nlm.nih.gov/clinvar/variation/55403/) This variant creates a premature stop codon at amino acid position 1703 of the BRCA1 protein and is thus predicted to result in a loss of function of the protein. The variant has not been detected in the ExAC database. This variant thus classified as pathogenic and actionable. (less)
|
|
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Pathogenic
(Sep 16, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000489268.2
First in ClinVar: Nov 05, 2016 Last updated: Dec 24, 2022 |
|
|
|
Pathogenic
(Mar 14, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000887713.3
First in ClinVar: Mar 13, 2019 Last updated: Dec 31, 2022 |
Comment:
This nonsense variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been reported in an individual affected with unilateral breast cancer … (more)
This nonsense variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been reported in an individual affected with unilateral breast cancer and individuals from hereditary breast and/or ovarian cancer families in the published literature (PMIDs: 26022348 (2015), 29446198 (2018), and 12491499 (2003)). Therefore, the variant is classified as pathogenic. (less)
|
|
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Pathogenic
(Nov 25, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003809768.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
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Pathogenic
(Dec 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000688537.4
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant changes 1 nucleotide in exon 17 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 17 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 in individuals affected with hereditary breast and ovarian cancer (PMID: 11748305, 12491499, 19941162). This variant has not been identified 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)
|
|
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Pathogenic
(Dec 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000076810.14
First in ClinVar: Jul 03, 2013 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Tyr1703*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Tyr1703*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 11748305, 12491499, 19941162). This variant is also known as 5228T>G. ClinVar contains an entry for this variant (Variation ID: 55403). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Jul 28, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000213370.7
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The p.Y1703* pathogenic mutation (also known as c.5109T>G), located in coding exon 16 of the BRCA1 gene, results from a T to G substitution at … (more)
The p.Y1703* pathogenic mutation (also known as c.5109T>G), located in coding exon 16 of the BRCA1 gene, results from a T to G substitution at nucleotide position 5109. This changes the amino acid from a tyrosine to a stop codon within coding exon 16. This mutation has been reported in patients with breast cancer (Adem C et al. Cancer. 2003 Jan;97:1-11; Tutt A et al. Lancet. 2010 Jul;376:235-44). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Dec 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004216918.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447741.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Breast carcinoma (present)
Sex: female
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Pathogenic
(Oct 25, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000916776.2
First in ClinVar: Jun 03, 2019 Last updated: Nov 20, 2021 |
Comment:
Variant summary: BRCA1 c.5109T>G (p.Tyr1703X) 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.5109T>G (p.Tyr1703X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251312 control chromosomes. c.5109T>G has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Judkins_2005, Tutt_2010,Adem_2002, Schroeder_2015, Eng_2001, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. 11 clinical diagnostic laboratories, including 1 expert panel and 1 consortium, have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Oct 02, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
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Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000326157.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Jul 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000210199.14
First in ClinVar: Feb 24, 2015 Last updated: Sep 16, 2024 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (PMID: 11748305, 12491499, 19941162); Published functional studies demonstrate a damaging effect: variant classified as non-functional based on a saturation genome editing (SGE) assay measuring cell survival (PMID: 30209399); 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 5228T>G; This variant is associated with the following publications: (PMID: 11748305, 36623239, 32191290, 25525159, 19941162, 20609467, 12491499, 16267036, 12048272, 31892343, 34308104, 26022348, 26295337, 20104584, 29446198, 28888541, 31447099, 31853058, 30209399) (less)
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Pathogenic
(May 29, 2002)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145316.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 4
Observation 2:
Number of individuals with the variant: 2
Geographic origin: Western European
Observation 3:
Number of individuals with the variant: 1
Geographic origin: Western, Central/Eastern European
Observation 4:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European
Observation 5:
Number of individuals with the variant: 1
Ethnicity/Population group: Native American, Central/Eastern European
Observation 6:
Number of individuals with the variant: 9
Ethnicity/Population group: Western European
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Pathogenic
(Jul 18, 2012)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000109400.2
First in ClinVar: Dec 23, 2013 Last updated: Sep 27, 2014 |
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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: SCV000587465.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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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: SCV001244108.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-2.17137513987016
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Comment:
Comment:
The c.5109T>G (p.Tyr1703*) variant has been reported in 18 patients in the Breast Cancer Information Core database. This variant was also reported in multiple patients in ClinVar and classified as a pathogenic variant by an expert panel (https://www.ncbi.nlm.nih.gov/clinvar/variation/55403/) This variant creates a premature stop codon at amino acid position 1703 of the BRCA1 protein and is thus predicted to result in a loss of function of the protein. The variant has not been detected in the ExAC database. This variant thus classified as pathogenic and actionable.
Comment:
This nonsense variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been reported in an individual affected with unilateral breast cancer and individuals from hereditary breast and/or ovarian cancer families in the published literature (PMIDs: 26022348 (2015), 29446198 (2018), and 12491499 (2003)). Therefore, the variant is classified as pathogenic.
Comment:
This variant changes 1 nucleotide in exon 17 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 in individuals affected with hereditary breast and ovarian cancer (PMID: 11748305, 12491499, 19941162). This variant has not been identified 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.
Comment:
This sequence change creates a premature translational stop signal (p.Tyr1703*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 11748305, 12491499, 19941162). This variant is also known as 5228T>G. ClinVar contains an entry for this variant (Variation ID: 55403). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.Y1703* pathogenic mutation (also known as c.5109T>G), located in coding exon 16 of the BRCA1 gene, results from a T to G substitution at nucleotide position 5109. This changes the amino acid from a tyrosine to a stop codon within coding exon 16. This mutation has been reported in patients with breast cancer (Adem C et al. Cancer. 2003 Jan;97:1-11; Tutt A et al. Lancet. 2010 Jul;376:235-44). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
Variant summary: BRCA1 c.5109T>G (p.Tyr1703X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251312 control chromosomes. c.5109T>G has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Judkins_2005, Tutt_2010,Adem_2002, Schroeder_2015, Eng_2001, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. 11 clinical diagnostic laboratories, including 1 expert panel and 1 consortium, have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (PMID: 11748305, 12491499, 19941162); Published functional studies demonstrate a damaging effect: variant classified as non-functional based on a saturation genome editing (SGE) assay measuring cell survival (PMID: 30209399); 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 5228T>G; This variant is associated with the following publications: (PMID: 11748305, 36623239, 32191290, 25525159, 19941162, 20609467, 12491499, 16267036, 12048272, 31892343, 34308104, 26022348, 26295337, 20104584, 29446198, 28888541, 31447099, 31853058, 30209399)
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: SCV001244108.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5109T>G, a NONSENSE variant, produced a function score of -2.17, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5109T>G, a NONSENSE variant, produced a function score of -2.17, 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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Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
The c.5109T>G (p.Tyr1703*) variant has been reported in 18 patients in the Breast Cancer Information Core database. This variant was also reported in multiple patients in ClinVar and classified as a pathogenic variant by an expert panel (https://www.ncbi.nlm.nih.gov/clinvar/variation/55403/) This variant creates a premature stop codon at amino acid position 1703 of the BRCA1 protein and is thus predicted to result in a loss of function of the protein. The variant has not been detected in the ExAC database. This variant thus classified as pathogenic and actionable.
Comment:
This nonsense variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been reported in an individual affected with unilateral breast cancer and individuals from hereditary breast and/or ovarian cancer families in the published literature (PMIDs: 26022348 (2015), 29446198 (2018), and 12491499 (2003)). Therefore, the variant is classified as pathogenic.
Comment:
This variant changes 1 nucleotide in exon 17 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 in individuals affected with hereditary breast and ovarian cancer (PMID: 11748305, 12491499, 19941162). This variant has not been identified 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.
Comment:
This sequence change creates a premature translational stop signal (p.Tyr1703*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 11748305, 12491499, 19941162). This variant is also known as 5228T>G. ClinVar contains an entry for this variant (Variation ID: 55403). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.Y1703* pathogenic mutation (also known as c.5109T>G), located in coding exon 16 of the BRCA1 gene, results from a T to G substitution at nucleotide position 5109. This changes the amino acid from a tyrosine to a stop codon within coding exon 16. This mutation has been reported in patients with breast cancer (Adem C et al. Cancer. 2003 Jan;97:1-11; Tutt A et al. Lancet. 2010 Jul;376:235-44). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
Variant summary: BRCA1 c.5109T>G (p.Tyr1703X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251312 control chromosomes. c.5109T>G has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Judkins_2005, Tutt_2010,Adem_2002, Schroeder_2015, Eng_2001, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. 11 clinical diagnostic laboratories, including 1 expert panel and 1 consortium, have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (PMID: 11748305, 12491499, 19941162); Published functional studies demonstrate a damaging effect: variant classified as non-functional based on a saturation genome editing (SGE) assay measuring cell survival (PMID: 30209399); 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 5228T>G; This variant is associated with the following publications: (PMID: 11748305, 36623239, 32191290, 25525159, 19941162, 20609467, 12491499, 16267036, 12048272, 31892343, 34308104, 26022348, 26295337, 20104584, 29446198, 28888541, 31447099, 31853058, 30209399)
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| Development and Validation of a Next-Generation Sequencing Assay for BRCA1 and BRCA2 Variants for the Clinical Laboratory. | Strom CM | PloS one | 2015 | PMID: 26295337 |
| HBOC multi-gene panel testing: comparison of two sequencing centers. | Schroeder C | Breast cancer research and treatment | 2015 | PMID: 26022348 |
| Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. | Tutt A | Lancet (London, England) | 2010 | PMID: 20609467 |
| 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 |
| High-throughput resequencing in the diagnosis of BRCA1/2 mutations using oligonucleotide resequencing microarrays. | Schroeder C | Breast cancer research and treatment | 2010 | PMID: 19941162 |
| Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. | Judkins T | Cancer research | 2005 | PMID: 16267036 |
| Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers. | Adem C | Cancer | 2003 | PMID: 12491499 |
| Pretest prediction of BRCA1 or BRCA2 mutation by risk counselors and the computer model BRCAPRO. | Euhus DM | Journal of the National Cancer Institute | 2002 | PMID: 12048272 |
| Interpreting epidemiological research: blinded comparison of methods used to estimate the prevalence of inherited mutations in BRCA1. | Eng C | Journal of medical genetics | 2001 | PMID: 11748305 |
| https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
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Text-mined citations for rs80356974 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 10, 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.