ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5497G>A (p.Val1833Met)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5497G>A (p.Val1833Met)
Variation ID: 55598 Accession: VCV000055598.26
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43045773 (GRCh38) [ NCBI UCSC ] 17: 41197790 (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 Aug 11, 2024 May 17, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.5497G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Val1833Met missense NM_001407571.1:c.5284G>A NP_001394500.1:p.Val1762Met missense NM_001407581.1:c.5563G>A NP_001394510.1:p.Val1855Met missense NM_001407582.1:c.5563G>A NP_001394511.1:p.Val1855Met missense NM_001407583.1:c.5560G>A NP_001394512.1:p.Val1854Met missense NM_001407585.1:c.5560G>A NP_001394514.1:p.Val1854Met missense NM_001407587.1:c.5560G>A NP_001394516.1:p.Val1854Met missense NM_001407590.1:c.5557G>A NP_001394519.1:p.Val1853Met missense NM_001407591.1:c.5557G>A NP_001394520.1:p.Val1853Met missense NM_001407593.1:c.5497G>A NP_001394522.1:p.Val1833Met missense NM_001407594.1:c.5497G>A NP_001394523.1:p.Val1833Met missense NM_001407596.1:c.5497G>A NP_001394525.1:p.Val1833Met missense NM_001407597.1:c.5497G>A NP_001394526.1:p.Val1833Met missense NM_001407598.1:c.5497G>A NP_001394527.1:p.Val1833Met missense NM_001407602.1:c.5497G>A NP_001394531.1:p.Val1833Met missense NM_001407603.1:c.5497G>A NP_001394532.1:p.Val1833Met missense NM_001407605.1:c.5497G>A NP_001394534.1:p.Val1833Met missense NM_001407610.1:c.5494G>A NP_001394539.1:p.Val1832Met missense NM_001407611.1:c.5494G>A NP_001394540.1:p.Val1832Met missense NM_001407612.1:c.5494G>A NP_001394541.1:p.Val1832Met missense NM_001407613.1:c.5494G>A NP_001394542.1:p.Val1832Met missense NM_001407614.1:c.5494G>A NP_001394543.1:p.Val1832Met missense NM_001407615.1:c.5494G>A NP_001394544.1:p.Val1832Met missense NM_001407616.1:c.5494G>A NP_001394545.1:p.Val1832Met missense NM_001407617.1:c.5494G>A NP_001394546.1:p.Val1832Met missense NM_001407618.1:c.5494G>A NP_001394547.1:p.Val1832Met missense NM_001407619.1:c.5494G>A NP_001394548.1:p.Val1832Met missense NM_001407620.1:c.5494G>A NP_001394549.1:p.Val1832Met missense NM_001407621.1:c.5494G>A NP_001394550.1:p.Val1832Met missense NM_001407622.1:c.5494G>A NP_001394551.1:p.Val1832Met missense NM_001407623.1:c.5494G>A NP_001394552.1:p.Val1832Met missense NM_001407624.1:c.5494G>A NP_001394553.1:p.Val1832Met missense NM_001407625.1:c.5494G>A NP_001394554.1:p.Val1832Met missense NM_001407626.1:c.5494G>A NP_001394555.1:p.Val1832Met missense NM_001407627.1:c.5491G>A NP_001394556.1:p.Val1831Met missense NM_001407628.1:c.5491G>A NP_001394557.1:p.Val1831Met missense NM_001407629.1:c.5491G>A NP_001394558.1:p.Val1831Met missense NM_001407630.1:c.5491G>A NP_001394559.1:p.Val1831Met missense NM_001407631.1:c.5491G>A NP_001394560.1:p.Val1831Met missense NM_001407632.1:c.5491G>A NP_001394561.1:p.Val1831Met missense NM_001407633.1:c.5491G>A NP_001394562.1:p.Val1831Met missense NM_001407634.1:c.5491G>A NP_001394563.1:p.Val1831Met missense NM_001407635.1:c.5491G>A NP_001394564.1:p.Val1831Met missense NM_001407636.1:c.5491G>A NP_001394565.1:p.Val1831Met missense NM_001407637.1:c.5491G>A NP_001394566.1:p.Val1831Met missense NM_001407638.1:c.5491G>A NP_001394567.1:p.Val1831Met missense NM_001407639.1:c.5491G>A NP_001394568.1:p.Val1831Met missense NM_001407640.1:c.5491G>A NP_001394569.1:p.Val1831Met missense NM_001407641.1:c.5491G>A NP_001394570.1:p.Val1831Met missense NM_001407642.1:c.5491G>A NP_001394571.1:p.Val1831Met missense NM_001407644.1:c.5488G>A NP_001394573.1:p.Val1830Met missense NM_001407645.1:c.5488G>A NP_001394574.1:p.Val1830Met missense NM_001407646.1:c.5485G>A NP_001394575.1:p.Val1829Met missense NM_001407647.1:c.5482G>A NP_001394576.1:p.Val1828Met missense NM_001407648.1:c.5440G>A NP_001394577.1:p.Val1814Met missense NM_001407649.1:c.5437G>A NP_001394578.1:p.Val1813Met missense NM_001407652.1:c.5419G>A NP_001394581.1:p.Val1807Met missense NM_001407653.1:c.5419G>A NP_001394582.1:p.Val1807Met missense NM_001407654.1:c.5419G>A NP_001394583.1:p.Val1807Met missense NM_001407655.1:c.5419G>A NP_001394584.1:p.Val1807Met missense NM_001407656.1:c.5416G>A NP_001394585.1:p.Val1806Met missense NM_001407657.1:c.5416G>A NP_001394586.1:p.Val1806Met missense NM_001407658.1:c.5416G>A NP_001394587.1:p.Val1806Met missense NM_001407659.1:c.5413G>A NP_001394588.1:p.Val1805Met missense NM_001407660.1:c.5413G>A NP_001394589.1:p.Val1805Met missense NM_001407661.1:c.5413G>A NP_001394590.1:p.Val1805Met missense NM_001407662.1:c.5413G>A NP_001394591.1:p.Val1805Met missense NM_001407663.1:c.5413G>A NP_001394592.1:p.Val1805Met missense NM_001407664.1:c.5374G>A NP_001394593.1:p.Val1792Met missense NM_001407665.1:c.5374G>A NP_001394594.1:p.Val1792Met missense NM_001407666.1:c.5374G>A NP_001394595.1:p.Val1792Met missense NM_001407667.1:c.5374G>A NP_001394596.1:p.Val1792Met missense NM_001407668.1:c.5374G>A NP_001394597.1:p.Val1792Met missense NM_001407669.1:c.5374G>A NP_001394598.1:p.Val1792Met missense NM_001407670.1:c.5371G>A NP_001394599.1:p.Val1791Met missense NM_001407671.1:c.5371G>A NP_001394600.1:p.Val1791Met missense NM_001407672.1:c.5371G>A NP_001394601.1:p.Val1791Met missense NM_001407673.1:c.5371G>A NP_001394602.1:p.Val1791Met missense NM_001407674.1:c.5371G>A NP_001394603.1:p.Val1791Met missense NM_001407675.1:c.5371G>A NP_001394604.1:p.Val1791Met missense NM_001407676.1:c.5371G>A NP_001394605.1:p.Val1791Met missense NM_001407677.1:c.5371G>A NP_001394606.1:p.Val1791Met missense NM_001407678.1:c.5371G>A NP_001394607.1:p.Val1791Met missense NM_001407679.1:c.5371G>A NP_001394608.1:p.Val1791Met missense NM_001407680.1:c.5371G>A NP_001394609.1:p.Val1791Met missense NM_001407681.1:c.5368G>A NP_001394610.1:p.Val1790Met missense NM_001407682.1:c.5368G>A NP_001394611.1:p.Val1790Met missense NM_001407683.1:c.5368G>A NP_001394612.1:p.Val1790Met missense NM_001407684.1:c.5368G>A NP_001394613.1:p.Val1790Met missense NM_001407685.1:c.5368G>A NP_001394614.1:p.Val1790Met missense NM_001407686.1:c.5368G>A NP_001394615.1:p.Val1790Met missense NM_001407687.1:c.5368G>A NP_001394616.1:p.Val1790Met missense NM_001407688.1:c.5368G>A NP_001394617.1:p.Val1790Met missense NM_001407689.1:c.5368G>A NP_001394618.1:p.Val1790Met missense NM_001407690.1:c.5365G>A NP_001394619.1:p.Val1789Met missense NM_001407691.1:c.5365G>A NP_001394620.1:p.Val1789Met missense NM_001407692.1:c.5356G>A NP_001394621.1:p.Val1786Met missense NM_001407694.1:c.5356G>A NP_001394623.1:p.Val1786Met missense NM_001407695.1:c.5356G>A NP_001394624.1:p.Val1786Met missense NM_001407696.1:c.5356G>A NP_001394625.1:p.Val1786Met missense NM_001407697.1:c.5356G>A NP_001394626.1:p.Val1786Met missense NM_001407698.1:c.5356G>A NP_001394627.1:p.Val1786Met missense NM_001407724.1:c.5356G>A NP_001394653.1:p.Val1786Met missense NM_001407725.1:c.5356G>A NP_001394654.1:p.Val1786Met missense NM_001407726.1:c.5356G>A NP_001394655.1:p.Val1786Met missense NM_001407727.1:c.5356G>A NP_001394656.1:p.Val1786Met missense NM_001407728.1:c.5356G>A NP_001394657.1:p.Val1786Met missense NM_001407729.1:c.5356G>A NP_001394658.1:p.Val1786Met missense NM_001407730.1:c.5356G>A NP_001394659.1:p.Val1786Met missense NM_001407731.1:c.5356G>A NP_001394660.1:p.Val1786Met missense NM_001407732.1:c.5353G>A NP_001394661.1:p.Val1785Met missense NM_001407733.1:c.5353G>A NP_001394662.1:p.Val1785Met missense NM_001407734.1:c.5353G>A NP_001394663.1:p.Val1785Met missense NM_001407735.1:c.5353G>A NP_001394664.1:p.Val1785Met missense NM_001407736.1:c.5353G>A NP_001394665.1:p.Val1785Met missense NM_001407737.1:c.5353G>A NP_001394666.1:p.Val1785Met missense NM_001407738.1:c.5353G>A NP_001394667.1:p.Val1785Met missense NM_001407739.1:c.5353G>A NP_001394668.1:p.Val1785Met missense NM_001407740.1:c.5353G>A NP_001394669.1:p.Val1785Met missense NM_001407741.1:c.5353G>A NP_001394670.1:p.Val1785Met missense NM_001407742.1:c.5353G>A NP_001394671.1:p.Val1785Met missense NM_001407743.1:c.5353G>A NP_001394672.1:p.Val1785Met missense NM_001407744.1:c.5353G>A NP_001394673.1:p.Val1785Met missense NM_001407745.1:c.5353G>A NP_001394674.1:p.Val1785Met missense NM_001407746.1:c.5353G>A NP_001394675.1:p.Val1785Met missense NM_001407747.1:c.5353G>A NP_001394676.1:p.Val1785Met missense NM_001407748.1:c.5353G>A NP_001394677.1:p.Val1785Met missense NM_001407749.1:c.5353G>A NP_001394678.1:p.Val1785Met missense NM_001407750.1:c.5353G>A NP_001394679.1:p.Val1785Met missense NM_001407751.1:c.5353G>A NP_001394680.1:p.Val1785Met missense NM_001407752.1:c.5353G>A NP_001394681.1:p.Val1785Met missense NM_001407838.1:c.5350G>A NP_001394767.1:p.Val1784Met missense NM_001407839.1:c.5350G>A NP_001394768.1:p.Val1784Met missense NM_001407841.1:c.5350G>A NP_001394770.1:p.Val1784Met missense NM_001407842.1:c.5350G>A NP_001394771.1:p.Val1784Met missense NM_001407843.1:c.5350G>A NP_001394772.1:p.Val1784Met missense NM_001407844.1:c.5350G>A NP_001394773.1:p.Val1784Met missense NM_001407845.1:c.5350G>A NP_001394774.1:p.Val1784Met missense NM_001407846.1:c.5350G>A NP_001394775.1:p.Val1784Met missense NM_001407847.1:c.5350G>A NP_001394776.1:p.Val1784Met missense NM_001407848.1:c.5350G>A NP_001394777.1:p.Val1784Met missense NM_001407849.1:c.5350G>A NP_001394778.1:p.Val1784Met missense NM_001407850.1:c.5350G>A NP_001394779.1:p.Val1784Met missense NM_001407851.1:c.5350G>A NP_001394780.1:p.Val1784Met missense NM_001407852.1:c.5350G>A NP_001394781.1:p.Val1784Met missense NM_001407853.1:c.5350G>A NP_001394782.1:p.Val1784Met missense NM_001407854.1:c.*11G>A NM_001407858.1:c.*11G>A NM_001407859.1:c.*11G>A NM_001407860.1:c.*11G>A NM_001407861.1:c.*11G>A NM_001407862.1:c.5296G>A NP_001394791.1:p.Val1766Met missense NM_001407863.1:c.5293G>A NP_001394792.1:p.Val1765Met missense NM_001407874.1:c.5290G>A NP_001394803.1:p.Val1764Met missense NM_001407875.1:c.5290G>A NP_001394804.1:p.Val1764Met missense NM_001407879.1:c.5287G>A NP_001394808.1:p.Val1763Met missense NM_001407881.1:c.5287G>A NP_001394810.1:p.Val1763Met missense NM_001407882.1:c.5287G>A NP_001394811.1:p.Val1763Met missense NM_001407884.1:c.5287G>A NP_001394813.1:p.Val1763Met missense NM_001407885.1:c.5287G>A NP_001394814.1:p.Val1763Met missense NM_001407886.1:c.5287G>A NP_001394815.1:p.Val1763Met missense NM_001407887.1:c.5287G>A NP_001394816.1:p.Val1763Met missense NM_001407889.1:c.5287G>A NP_001394818.1:p.Val1763Met missense NM_001407894.1:c.5284G>A NP_001394823.1:p.Val1762Met missense NM_001407895.1:c.5284G>A NP_001394824.1:p.Val1762Met missense NM_001407896.1:c.5284G>A NP_001394825.1:p.Val1762Met missense NM_001407897.1:c.5284G>A NP_001394826.1:p.Val1762Met missense NM_001407898.1:c.5284G>A NP_001394827.1:p.Val1762Met missense NM_001407899.1:c.5284G>A NP_001394828.1:p.Val1762Met missense NM_001407900.1:c.5284G>A NP_001394829.1:p.Val1762Met missense NM_001407902.1:c.5284G>A NP_001394831.1:p.Val1762Met missense NM_001407904.1:c.5284G>A NP_001394833.1:p.Val1762Met missense NM_001407906.1:c.5284G>A NP_001394835.1:p.Val1762Met missense NM_001407907.1:c.5284G>A NP_001394836.1:p.Val1762Met missense NM_001407908.1:c.5284G>A NP_001394837.1:p.Val1762Met missense NM_001407909.1:c.5284G>A NP_001394838.1:p.Val1762Met missense NM_001407910.1:c.5284G>A NP_001394839.1:p.Val1762Met missense NM_001407915.1:c.5281G>A NP_001394844.1:p.Val1761Met missense NM_001407916.1:c.5281G>A NP_001394845.1:p.Val1761Met missense NM_001407917.1:c.5281G>A NP_001394846.1:p.Val1761Met missense NM_001407918.1:c.5281G>A NP_001394847.1:p.Val1761Met missense NM_001407919.1:c.5245G>A NP_001394848.1:p.Val1749Met missense NM_001407920.1:c.5233G>A NP_001394849.1:p.Val1745Met missense NM_001407921.1:c.5233G>A NP_001394850.1:p.Val1745Met missense NM_001407922.1:c.5233G>A NP_001394851.1:p.Val1745Met missense NM_001407923.1:c.5233G>A NP_001394852.1:p.Val1745Met missense NM_001407924.1:c.5233G>A NP_001394853.1:p.Val1745Met missense NM_001407925.1:c.5233G>A NP_001394854.1:p.Val1745Met missense NM_001407926.1:c.5233G>A NP_001394855.1:p.Val1745Met missense NM_001407927.1:c.5230G>A NP_001394856.1:p.Val1744Met missense NM_001407928.1:c.5230G>A NP_001394857.1:p.Val1744Met missense NM_001407929.1:c.5230G>A NP_001394858.1:p.Val1744Met missense NM_001407930.1:c.5230G>A NP_001394859.1:p.Val1744Met missense NM_001407931.1:c.5230G>A NP_001394860.1:p.Val1744Met missense NM_001407932.1:c.5230G>A NP_001394861.1:p.Val1744Met missense NM_001407933.1:c.5230G>A NP_001394862.1:p.Val1744Met missense NM_001407934.1:c.5227G>A NP_001394863.1:p.Val1743Met missense NM_001407935.1:c.5227G>A NP_001394864.1:p.Val1743Met missense NM_001407936.1:c.5227G>A NP_001394865.1:p.Val1743Met missense NM_001407937.1:c.*11G>A NM_001407938.1:c.*11G>A NM_001407939.1:c.*11G>A NM_001407940.1:c.*11G>A NM_001407941.1:c.*11G>A NM_001407942.1:c.*11G>A NM_001407943.1:c.*11G>A NM_001407944.1:c.*11G>A NM_001407945.1:c.*11G>A NM_001407946.1:c.5164G>A NP_001394875.1:p.Val1722Met missense NM_001407947.1:c.5164G>A NP_001394876.1:p.Val1722Met missense NM_001407948.1:c.5164G>A NP_001394877.1:p.Val1722Met missense NM_001407949.1:c.5164G>A NP_001394878.1:p.Val1722Met missense NM_001407950.1:c.5161G>A NP_001394879.1:p.Val1721Met missense NM_001407951.1:c.5161G>A NP_001394880.1:p.Val1721Met missense NM_001407952.1:c.5161G>A NP_001394881.1:p.Val1721Met missense NM_001407953.1:c.5161G>A NP_001394882.1:p.Val1721Met missense NM_001407954.1:c.5161G>A NP_001394883.1:p.Val1721Met missense NM_001407955.1:c.5161G>A NP_001394884.1:p.Val1721Met missense NM_001407956.1:c.5158G>A NP_001394885.1:p.Val1720Met missense NM_001407957.1:c.5158G>A NP_001394886.1:p.Val1720Met missense NM_001407958.1:c.5158G>A NP_001394887.1:p.Val1720Met missense NM_001407959.1:c.5116G>A NP_001394888.1:p.Val1706Met missense NM_001407960.1:c.5113G>A NP_001394889.1:p.Val1705Met missense NM_001407962.1:c.5113G>A NP_001394891.1:p.Val1705Met missense NM_001407963.1:c.5110G>A NP_001394892.1:p.Val1704Met missense NM_001407964.1:c.5035G>A NP_001394893.1:p.Val1679Met missense NM_001407965.1:c.4990G>A NP_001394894.1:p.Val1664Met missense NM_001407966.1:c.4609G>A NP_001394895.1:p.Val1537Met missense NM_001407967.1:c.4606G>A NP_001394896.1:p.Val1536Met missense NM_001407968.1:c.2893G>A NP_001394897.1:p.Val965Met missense NM_001407969.1:c.2890G>A NP_001394898.1:p.Val964Met missense NM_001407970.1:c.2254G>A NP_001394899.1:p.Val752Met missense NM_001407971.1:c.2254G>A NP_001394900.1:p.Val752Met missense NM_001407972.1:c.2251G>A NP_001394901.1:p.Val751Met missense NM_001407973.1:c.2188G>A NP_001394902.1:p.Val730Met missense NM_001407974.1:c.2188G>A NP_001394903.1:p.Val730Met missense NM_001407975.1:c.2188G>A NP_001394904.1:p.Val730Met missense NM_001407976.1:c.2188G>A NP_001394905.1:p.Val730Met missense NM_001407977.1:c.2188G>A NP_001394906.1:p.Val730Met missense NM_001407978.1:c.2188G>A NP_001394907.1:p.Val730Met missense NM_001407979.1:c.2185G>A NP_001394908.1:p.Val729Met missense NM_001407980.1:c.2185G>A NP_001394909.1:p.Val729Met missense NM_001407981.1:c.2185G>A NP_001394910.1:p.Val729Met missense NM_001407982.1:c.2185G>A NP_001394911.1:p.Val729Met missense NM_001407983.1:c.2185G>A NP_001394912.1:p.Val729Met missense NM_001407984.1:c.2185G>A NP_001394913.1:p.Val729Met missense NM_001407985.1:c.2185G>A NP_001394914.1:p.Val729Met missense NM_001407986.1:c.2185G>A NP_001394915.1:p.Val729Met missense NM_001407990.1:c.2185G>A NP_001394919.1:p.Val729Met missense NM_001407991.1:c.2185G>A NP_001394920.1:p.Val729Met missense NM_001407992.1:c.2185G>A NP_001394921.1:p.Val729Met missense NM_001407993.1:c.2185G>A NP_001394922.1:p.Val729Met missense NM_001408392.1:c.2182G>A NP_001395321.1:p.Val728Met missense NM_001408396.1:c.2182G>A NP_001395325.1:p.Val728Met missense NM_001408397.1:c.2182G>A NP_001395326.1:p.Val728Met missense NM_001408398.1:c.2182G>A NP_001395327.1:p.Val728Met missense NM_001408399.1:c.2182G>A NP_001395328.1:p.Val728Met missense NM_001408400.1:c.2182G>A NP_001395329.1:p.Val728Met missense NM_001408401.1:c.2182G>A NP_001395330.1:p.Val728Met missense NM_001408402.1:c.2182G>A NP_001395331.1:p.Val728Met missense NM_001408403.1:c.2182G>A NP_001395332.1:p.Val728Met missense NM_001408404.1:c.2182G>A NP_001395333.1:p.Val728Met missense NM_001408406.1:c.2179G>A NP_001395335.1:p.Val727Met missense NM_001408407.1:c.2179G>A NP_001395336.1:p.Val727Met missense NM_001408408.1:c.2179G>A NP_001395337.1:p.Val727Met missense NM_001408409.1:c.2176G>A NP_001395338.1:p.Val726Met missense NM_001408410.1:c.2113G>A NP_001395339.1:p.Val705Met missense NM_001408411.1:c.2110G>A NP_001395340.1:p.Val704Met missense NM_001408412.1:c.2107G>A NP_001395341.1:p.Val703Met missense NM_001408413.1:c.2107G>A NP_001395342.1:p.Val703Met missense NM_001408414.1:c.2107G>A NP_001395343.1:p.Val703Met missense NM_001408415.1:c.2107G>A NP_001395344.1:p.Val703Met missense NM_001408416.1:c.2107G>A NP_001395345.1:p.Val703Met missense NM_001408418.1:c.2071G>A NP_001395347.1:p.Val691Met missense NM_001408419.1:c.2071G>A NP_001395348.1:p.Val691Met missense NM_001408420.1:c.2071G>A NP_001395349.1:p.Val691Met missense NM_001408421.1:c.2068G>A NP_001395350.1:p.Val690Met missense NM_001408422.1:c.2068G>A NP_001395351.1:p.Val690Met missense NM_001408423.1:c.2068G>A NP_001395352.1:p.Val690Met missense NM_001408424.1:c.2068G>A NP_001395353.1:p.Val690Met missense NM_001408425.1:c.2065G>A NP_001395354.1:p.Val689Met missense NM_001408426.1:c.2065G>A NP_001395355.1:p.Val689Met missense NM_001408427.1:c.2065G>A NP_001395356.1:p.Val689Met missense NM_001408428.1:c.2065G>A NP_001395357.1:p.Val689Met missense NM_001408429.1:c.2065G>A NP_001395358.1:p.Val689Met missense NM_001408430.1:c.2065G>A NP_001395359.1:p.Val689Met missense NM_001408431.1:c.2065G>A NP_001395360.1:p.Val689Met missense NM_001408432.1:c.2062G>A NP_001395361.1:p.Val688Met missense NM_001408433.1:c.2062G>A NP_001395362.1:p.Val688Met missense NM_001408434.1:c.2062G>A NP_001395363.1:p.Val688Met missense NM_001408435.1:c.2062G>A NP_001395364.1:p.Val688Met missense NM_001408436.1:c.2062G>A NP_001395365.1:p.Val688Met missense NM_001408437.1:c.2062G>A NP_001395366.1:p.Val688Met missense NM_001408438.1:c.2062G>A NP_001395367.1:p.Val688Met missense NM_001408439.1:c.2062G>A NP_001395368.1:p.Val688Met missense NM_001408440.1:c.2062G>A NP_001395369.1:p.Val688Met missense NM_001408441.1:c.2062G>A NP_001395370.1:p.Val688Met missense NM_001408442.1:c.2062G>A NP_001395371.1:p.Val688Met missense NM_001408443.1:c.2062G>A NP_001395372.1:p.Val688Met missense NM_001408444.1:c.2062G>A NP_001395373.1:p.Val688Met missense NM_001408445.1:c.2059G>A NP_001395374.1:p.Val687Met missense NM_001408446.1:c.2059G>A NP_001395375.1:p.Val687Met missense NM_001408447.1:c.2059G>A NP_001395376.1:p.Val687Met missense NM_001408448.1:c.2059G>A NP_001395377.1:p.Val687Met missense NM_001408450.1:c.2059G>A NP_001395379.1:p.Val687Met missense NM_001408451.1:c.2053G>A NP_001395380.1:p.Val685Met missense NM_001408452.1:c.2047G>A NP_001395381.1:p.Val683Met missense NM_001408453.1:c.2047G>A NP_001395382.1:p.Val683Met missense NM_001408454.1:c.2047G>A NP_001395383.1:p.Val683Met missense NM_001408455.1:c.2047G>A NP_001395384.1:p.Val683Met missense NM_001408456.1:c.2047G>A NP_001395385.1:p.Val683Met missense NM_001408457.1:c.2047G>A NP_001395386.1:p.Val683Met missense NM_001408458.1:c.2044G>A NP_001395387.1:p.Val682Met missense NM_001408459.1:c.2044G>A NP_001395388.1:p.Val682Met missense NM_001408460.1:c.2044G>A NP_001395389.1:p.Val682Met missense NM_001408461.1:c.2044G>A NP_001395390.1:p.Val682Met missense NM_001408462.1:c.2044G>A NP_001395391.1:p.Val682Met missense NM_001408463.1:c.2044G>A NP_001395392.1:p.Val682Met missense NM_001408464.1:c.2044G>A NP_001395393.1:p.Val682Met missense NM_001408465.1:c.2044G>A NP_001395394.1:p.Val682Met missense NM_001408466.1:c.2044G>A NP_001395395.1:p.Val682Met missense NM_001408467.1:c.2044G>A NP_001395396.1:p.Val682Met missense NM_001408468.1:c.2041G>A NP_001395397.1:p.Val681Met missense NM_001408469.1:c.2041G>A NP_001395398.1:p.Val681Met missense NM_001408470.1:c.2041G>A NP_001395399.1:p.Val681Met missense NM_001408472.1:c.*11G>A NM_001408473.1:c.*11G>A NM_001408474.1:c.1987G>A NP_001395403.1:p.Val663Met missense NM_001408475.1:c.1984G>A NP_001395404.1:p.Val662Met missense NM_001408476.1:c.1984G>A NP_001395405.1:p.Val662Met missense NM_001408478.1:c.1978G>A NP_001395407.1:p.Val660Met missense NM_001408479.1:c.1978G>A NP_001395408.1:p.Val660Met missense NM_001408480.1:c.1978G>A NP_001395409.1:p.Val660Met missense NM_001408481.1:c.1975G>A NP_001395410.1:p.Val659Met missense NM_001408482.1:c.1975G>A NP_001395411.1:p.Val659Met missense NM_001408483.1:c.1975G>A NP_001395412.1:p.Val659Met missense NM_001408484.1:c.1975G>A NP_001395413.1:p.Val659Met missense NM_001408485.1:c.1975G>A NP_001395414.1:p.Val659Met missense NM_001408489.1:c.1975G>A NP_001395418.1:p.Val659Met missense NM_001408490.1:c.1975G>A NP_001395419.1:p.Val659Met missense NM_001408491.1:c.1975G>A NP_001395420.1:p.Val659Met missense NM_001408492.1:c.1972G>A NP_001395421.1:p.Val658Met missense NM_001408493.1:c.1972G>A NP_001395422.1:p.Val658Met missense NM_001408494.1:c.1948G>A NP_001395423.1:p.Val650Met missense NM_001408495.1:c.1942G>A NP_001395424.1:p.Val648Met missense NM_001408496.1:c.1924G>A NP_001395425.1:p.Val642Met missense NM_001408497.1:c.1924G>A NP_001395426.1:p.Val642Met missense NM_001408498.1:c.1924G>A NP_001395427.1:p.Val642Met missense NM_001408499.1:c.1924G>A NP_001395428.1:p.Val642Met missense NM_001408500.1:c.1924G>A NP_001395429.1:p.Val642Met missense NM_001408501.1:c.1924G>A NP_001395430.1:p.Val642Met missense NM_001408502.1:c.1921G>A NP_001395431.1:p.Val641Met missense NM_001408503.1:c.1921G>A NP_001395432.1:p.Val641Met missense NM_001408504.1:c.1921G>A NP_001395433.1:p.Val641Met missense NM_001408505.1:c.1918G>A NP_001395434.1:p.Val640Met missense NM_001408506.1:c.1861G>A NP_001395435.1:p.Val621Met missense NM_001408507.1:c.1858G>A NP_001395436.1:p.Val620Met missense NM_001408508.1:c.1849G>A NP_001395437.1:p.Val617Met missense NM_001408509.1:c.1846G>A NP_001395438.1:p.Val616Met missense NM_001408510.1:c.1807G>A NP_001395439.1:p.Val603Met missense NM_001408511.1:c.1804G>A NP_001395440.1:p.Val602Met missense NM_001408512.1:c.1684G>A NP_001395441.1:p.Val562Met missense NM_001408513.1:c.1657G>A NP_001395442.1:p.Val553Met missense NM_001408514.1:c.1261G>A NP_001395443.1:p.Val421Met missense NM_007297.4:c.5356G>A NP_009228.2:p.Val1786Met missense NM_007298.4:c.2185G>A NP_009229.2:p.Val729Met missense NM_007299.4:c.*11G>A 3 prime UTR NM_007300.4:c.5560G>A NP_009231.2:p.Val1854Met missense NM_007304.2:c.2185G>A NP_009235.2:p.Val729Met missense NR_027676.2:n.5674G>A non-coding transcript variant NC_000017.11:g.43045773C>T NC_000017.10:g.41197790C>T NG_005905.2:g.172211G>A LRG_292:g.172211G>A LRG_292t1:c.5497G>A LRG_292p1:p.Val1833Met U14680.1:n.5616G>A - Protein change
- V1833M, V1854M, V729M, V1786M, V1536M, V1722M, V1745M, V1761M, V1763M, V1764M, V1765M, V1784M, V1790M, V1807M, V1828M, V1830M, V1831M, V1853M, V553M, V617M, V621M, V642M, V659M, V683M, V689M, V703M, V704M, V752M, V965M, V1537M, V1664M, V1679M, V1720M, V1721M, V1749M, V1813M, V1829M, V1855M, V603M, V640M, V660M, V726M, V964M, V1706M, V1743M, V1744M, V1785M, V1789M, V1806M, V1814M, V1832M, V421M, V602M, V616M, V650M, V663M, V682M, V727M, V751M, V1704M, V1705M, V1762M, V1766M, V1791M, V1792M, V1805M, V562M, V620M, V641M, V648M, V658M, V662M, V681M, V685M, V687M, V688M, V690M, V691M, V705M, V728M, V730M
- Other names
- 5616G>A
- Canonical SPDI
- NC_000017.11:43045772:C:T
-
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.5497G>A, a MISSENSE variant, produced a function score of -2.18, 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.
The Genome Aggregation Database (gnomAD), exomes 0.00000
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 |
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/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Dec 21, 2023 | RCV000049017.17 | |
Likely pathogenic (5) |
criteria provided, single submitter
|
May 20, 2016 | RCV000077626.11 | |
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
May 17, 2024 | RCV000132307.12 | |
Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Oct 23, 2020 | RCV000255915.5 | |
Pathogenic (1) |
criteria provided, single submitter
|
May 4, 2022 | RCV002247446.2 |
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. |
|
---|---|---|---|---|---|
Likely pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Autosomal unknown)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447942.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Ovarian neoplasm (present)
Sex: female
|
|
Pathogenic
(Dec 21, 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: SCV000077030.11
First in ClinVar: Jul 03, 2013 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1833 of the BRCA1 protein (p.Val1833Met). … (more)
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1833 of the BRCA1 protein (p.Val1833Met). This variant is present in population databases (rs80357268, gnomAD 0.0009%). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 10923033, 12142080, 16284991, 23536787; Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as 5616G>A. ClinVar contains an entry for this variant (Variation ID: 55598). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 15004537, 17493881, 18992264, 20378548, 20516115, 20526115, 28781887, 30209399). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Likely pathogenic
(May 06, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000322039.7
First in ClinVar: Oct 09, 2016 Last updated: Oct 09, 2016 |
Comment:
This variant is denoted BRCA1 c.5497G>A at the cDNA level, p.Val1833Met (V1833M) at the protein level, and results in the change of a Valine to … (more)
This variant is denoted BRCA1 c.5497G>A at the cDNA level, p.Val1833Met (V1833M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). This variant, also published as BRCA1 5616G>A using alternate nomenclature, has been reported in association with breast and ovarian cancer (Ladopoulou 2002, Pal 2005, Stavropoulou 2013). While BRCA1 Val1833Met has been associated with binding activity similar to wild type, functional assays also report it significantly reduces, but does not destroy, transactivation activity in both yeast and human embryonic cell models, mildly to severely impacts protein thermostability, and abrogates the small colony phenotype in yeast (Coyne 2004, Nikolopoulos 2007, Carvalho 2009, Lee 2010, Rowling 2010). BRCA1 Val1833Met was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Valine and Methionine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Val1833Met occurs at a position that is conserved in mammals and is located within the BRCT2 domain and a region known to interact with multiple proteins (Paul 2014, UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on the currently available evidence, we consider BRCA1 Val1833Met to be a likely pathogenic variant. (less)
|
|
Likely pathogenic
(Jan 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
GeneKor MSA
Accession: SCV000693500.2
First in ClinVar: Dec 26, 2017 Last updated: May 04, 2020 |
Comment:
This sequence change replaces Valine with Methionine at codon 1833 of the BRCA1 protein. The Valine residue is highly conserved among species and it is … (more)
This sequence change replaces Valine with Methionine at codon 1833 of the BRCA1 protein. The Valine residue is highly conserved among species and it is located within the BRCT domain that is important for BRCA1 function. There is a small physiochemical difference between Valine and Methionine (Grantham Score 21). This variant is also known as 5616G>A and it has been reported in the literature in individuals and families with breast and/or ovarian cancer, with some evidence of segregation with disease in a single family (PMID: 23536787, 12142080). To our Knowledge, this variant is not present in population databases (rs80357268). The mutation database ClinVar contains entries for this variant (Variation ID: 55598). Algorithms developed to predict the effect of missense changes on protein structure and function suggest that this variant may be damaging to the protein. These predictions have been also confirmed by published functional studies. Experimental studies have shown that this missense change affects protein folding and stability, as well as functional activity of the BRCA1 protein (PMID: 18992264, 20378548). (less)
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Likely pathogenic
(May 20, 2016)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296422.2
First in ClinVar: May 27, 2015 Last updated: Jan 01, 2022 |
Indication for testing: Hereditary breast and ovarian cancer syndrome (HBOC)
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Pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
germline
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Mendelics
Accession: SCV002518585.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Pathogenic
(Nov 16, 2022)
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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: SCV000699266.3
First in ClinVar: Dec 26, 2017 Last updated: Dec 24, 2022 |
Comment:
Variant summary: BRCA1 c.5497G>A (p.Val1833Met) results in a conservative amino acid change located in the BRCT domain (IPR001357) of the encoded protein sequence. Four of … (more)
Variant summary: BRCA1 c.5497G>A (p.Val1833Met) results in a conservative amino acid change located in the BRCT domain (IPR001357) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. Several in silico studies also predict a deleterious outcome for the variant (Carvalho_2009, Karchin_2007, Pavlicek_2004, Zhang_1998). Functional studies are in agreement with these predictions demonstrating that although the variant confers normal binding activity, it results in considerably reduced transcriptional activity and destabilizes the protein (Carvalho_2009, Fernandes_2019, Lee_2010, Rowling_2010, Woods_2016). At least one functional study reports experimental evidence evaluating an impact on protein function a damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). HDR assays qualify as a recognized gold standard on the basis of updated guidance provided by the ClinGen Sequence Variant Interpretation (SVI) working group. The variant allele was found at a frequency of 4e-06 in 251228 control chromosomes (gnomAD). c.5497G>A has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer, including at least one family with evidence of co-segregation with disease (Fostira_2019, Judkins_2005, Kotoula_2017, Pal_2005, Stavropoulou_2013). These data indicate that the variant is very likely to be associated with disease. Eight ClinVar submitters (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(Oct 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV001355748.3
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces valine with methionine at codon 1833 of the BRCA1 protein. Computational prediction tool suggests that this variant may have deleterious impact … (more)
This missense variant replaces valine with methionine at codon 1833 of the BRCA1 protein. Computational prediction tool suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant impairs BRCA1 protein folding and stability, transcriptional activation, and ability to support haploid cell survival (PMID: 15004537, 17493881, 18992264, 20378548, 20526115, 28781887, 30209399). This variant is known to be a founder mutation in the Greek population (PMID: 31447071) and has been observed in many individuals affected with breast and ovarian cancer (PMID: 16284991, 23536787, 31447071). This variant has also been identified in 1/251228 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
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Likely pathogenic
(May 17, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000187393.10
First in ClinVar: Aug 06, 2014 Last updated: Aug 11, 2024 |
Comment:
The p.V1833M variant (also known as c.5497G>A), located in coding exon 22 of the BRCA1 gene, results from a G to A substitution at nucleotide … (more)
The p.V1833M variant (also known as c.5497G>A), located in coding exon 22 of the BRCA1 gene, results from a G to A substitution at nucleotide position 5497. The valine at codon 1833 is replaced by methionine, an amino acid with highly similar properties. This alteration has been found with enriched frequency in cohorts of Greek breast and/or ovarian cancer patients and segregated with disease in one kindred with familial ovarian cancer (Stavropoulou AV, PLoS ONE 2013; 8(3):e58182; Apessos A et al. Cancer Genet 2018 01;220:1-12; Papamentzelopoulou M et al. Cancer Genet. 2019 Sep;237:90-96). The work by Rowling et al., both experimentally and computationally showed the destabilization of the BRCT2 domain by this variant, significantly leading to unfolding and loss of function (Rowling PJ, J. Biol. Chem. 2010 Jun; 285(26):20080-7). Functional assays demonstrate reduced transactivation activity compared to wild-type (Carvalho M, Mutat. Res. 2009 Jan; 660(1-2):1-11, Woods et al, npj Genomic Medicine 1, Article number: 16001 (2016) doi:10.1038/npjgenmed.2016.1; Findlay GM et al. Nature 2018 10;562(7726):217-222). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
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Pathogenic
(Oct 15, 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: SCV000109429.2
First in ClinVar: Dec 23, 2013 Last updated: Sep 27, 2014 |
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Likely 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: SCV004243906.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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Uncertain significance
(Feb 20, 2004)
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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: SCV000145548.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: Greek
Geographic origin: Greece
Observation 4:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591635.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Number of individuals with the variant: 1
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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: SCV001243464.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-2.18348435841623
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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: SCV001243464.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5497G>A, a MISSENSE variant, produced a function score of -2.18, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5497G>A, a MISSENSE variant, produced a function score of -2.18, 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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One in three highly selected Greek patients with breast cancer carries a loss-of-function variant in a cancer susceptibility gene. | Fostira F | Journal of medical genetics | 2020 | PMID: 31300551 |
Prevalence and founder effect of the BRCA1 p.(Val1833Met) variant in the Greek population, with further evidence for pathogenicity and risk modification. | Papamentzelopoulou M | Cancer genetics | 2019 | PMID: 31447071 |
Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation. | Fernandes VC | The Journal of biological chemistry | 2019 | PMID: 30765603 |
Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
The fate of BRCA1-related germline mutations in triple-negative breast tumors. | Kotoula V | American journal of cancer research | 2017 | PMID: 28123851 |
Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance. | Woods NT | NPJ genomic medicine | 2016 | PMID: 28781887 |
Prevalence of BRCA1 mutations in familial and sporadic greek ovarian cancer cases. | Stavropoulou AV | PloS one | 2013 | PMID: 23536787 |
Nursing welcome mat to the hospital, an advanced practice nurse's responsibility. | Mwose J | Clinical nurse specialist CNS | 2010 | PMID: 20526115 |
Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. | Lee MS | Cancer research | 2010 | PMID: 20516115 |
Toward classification of BRCA1 missense variants using a biophysical approach. | Rowling PJ | The Journal of biological chemistry | 2010 | PMID: 20378548 |
Analysis of a set of missense, frameshift, and in-frame deletion variants of BRCA1. | Carvalho M | Mutation research | 2009 | PMID: 18992264 |
Thermal unfolding of human BRCA1 BRCT-domain variants. | Nikolopoulos G | Biochimica et biophysica acta | 2007 | PMID: 17493881 |
Functional impact of missense variants in BRCA1 predicted by supervised learning. | Karchin R | PLoS computational biology | 2007 | PMID: 17305420 |
BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. | Pal T | Cancer | 2005 | PMID: 16284991 |
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 |
Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition. | Pavlicek A | Human molecular genetics | 2004 | PMID: 15385441 |
Structure-based assessment of missense mutations in human BRCA1: implications for breast and ovarian cancer predisposition. | Mirkovic N | Cancer research | 2004 | PMID: 15172985 |
Functional characterization of BRCA1 sequence variants using a yeast small colony phenotype assay. | Coyne RS | Cancer biology & therapy | 2004 | PMID: 15004537 |
Germ line BRCA1 & BRCA2 mutations in Greek breast/ovarian cancer families: 5382insC is the most frequent mutation observed. | Ladopoulou A | Cancer letters | 2002 | PMID: 12142080 |
The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
Structure of an XRCC1 BRCT domain: a new protein-protein interaction module. | Zhang X | The EMBO journal | 1998 | PMID: 9799248 |
https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
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Text-mined citations for rs80357268 ...
HelpRecord last updated Oct 08, 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.