ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5349G>A (p.Met1783Ile)
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.
Uncertain significance(4); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.5349G>A (p.Met1783Ile)
Variation ID: 141796 Accession: VCV000141796.15
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43049178 (GRCh38) [ NCBI UCSC ] 17: 41201195 (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 Mar 24, 2015 May 1, 2024 Nov 9, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.5349G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Met1783Ile missense NM_001407571.1:c.5136G>A NP_001394500.1:p.Met1712Ile missense NM_001407581.1:c.5415G>A NP_001394510.1:p.Met1805Ile missense NM_001407582.1:c.5415G>A NP_001394511.1:p.Met1805Ile missense NM_001407583.1:c.5412G>A NP_001394512.1:p.Met1804Ile missense NM_001407585.1:c.5412G>A NP_001394514.1:p.Met1804Ile missense NM_001407587.1:c.5412G>A NP_001394516.1:p.Met1804Ile missense NM_001407590.1:c.5409G>A NP_001394519.1:p.Met1803Ile missense NM_001407591.1:c.5409G>A NP_001394520.1:p.Met1803Ile missense NM_001407593.1:c.5349G>A NP_001394522.1:p.Met1783Ile missense NM_001407594.1:c.5349G>A NP_001394523.1:p.Met1783Ile missense NM_001407596.1:c.5349G>A NP_001394525.1:p.Met1783Ile missense NM_001407597.1:c.5349G>A NP_001394526.1:p.Met1783Ile missense NM_001407598.1:c.5349G>A NP_001394527.1:p.Met1783Ile missense NM_001407602.1:c.5349G>A NP_001394531.1:p.Met1783Ile missense NM_001407603.1:c.5349G>A NP_001394532.1:p.Met1783Ile missense NM_001407605.1:c.5349G>A NP_001394534.1:p.Met1783Ile missense NM_001407610.1:c.5346G>A NP_001394539.1:p.Met1782Ile missense NM_001407611.1:c.5346G>A NP_001394540.1:p.Met1782Ile missense NM_001407612.1:c.5346G>A NP_001394541.1:p.Met1782Ile missense NM_001407613.1:c.5346G>A NP_001394542.1:p.Met1782Ile missense NM_001407614.1:c.5346G>A NP_001394543.1:p.Met1782Ile missense NM_001407615.1:c.5346G>A NP_001394544.1:p.Met1782Ile missense NM_001407616.1:c.5346G>A NP_001394545.1:p.Met1782Ile missense NM_001407617.1:c.5346G>A NP_001394546.1:p.Met1782Ile missense NM_001407618.1:c.5346G>A NP_001394547.1:p.Met1782Ile missense NM_001407619.1:c.5346G>A NP_001394548.1:p.Met1782Ile missense NM_001407620.1:c.5346G>A NP_001394549.1:p.Met1782Ile missense NM_001407621.1:c.5346G>A NP_001394550.1:p.Met1782Ile missense NM_001407622.1:c.5346G>A NP_001394551.1:p.Met1782Ile missense NM_001407623.1:c.5346G>A NP_001394552.1:p.Met1782Ile missense NM_001407624.1:c.5346G>A NP_001394553.1:p.Met1782Ile missense NM_001407625.1:c.5346G>A NP_001394554.1:p.Met1782Ile missense NM_001407626.1:c.5346G>A NP_001394555.1:p.Met1782Ile missense NM_001407627.1:c.5343G>A NP_001394556.1:p.Met1781Ile missense NM_001407628.1:c.5343G>A NP_001394557.1:p.Met1781Ile missense NM_001407629.1:c.5343G>A NP_001394558.1:p.Met1781Ile missense NM_001407630.1:c.5343G>A NP_001394559.1:p.Met1781Ile missense NM_001407631.1:c.5343G>A NP_001394560.1:p.Met1781Ile missense NM_001407632.1:c.5343G>A NP_001394561.1:p.Met1781Ile missense NM_001407633.1:c.5343G>A NP_001394562.1:p.Met1781Ile missense NM_001407634.1:c.5343G>A NP_001394563.1:p.Met1781Ile missense NM_001407635.1:c.5343G>A NP_001394564.1:p.Met1781Ile missense NM_001407636.1:c.5343G>A NP_001394565.1:p.Met1781Ile missense NM_001407637.1:c.5343G>A NP_001394566.1:p.Met1781Ile missense NM_001407638.1:c.5343G>A NP_001394567.1:p.Met1781Ile missense NM_001407639.1:c.5343G>A NP_001394568.1:p.Met1781Ile missense NM_001407640.1:c.5343G>A NP_001394569.1:p.Met1781Ile missense NM_001407641.1:c.5343G>A NP_001394570.1:p.Met1781Ile missense NM_001407642.1:c.5343G>A NP_001394571.1:p.Met1781Ile missense NM_001407644.1:c.5340G>A NP_001394573.1:p.Met1780Ile missense NM_001407645.1:c.5340G>A NP_001394574.1:p.Met1780Ile missense NM_001407646.1:c.5337G>A NP_001394575.1:p.Met1779Ile missense NM_001407647.1:c.5334G>A NP_001394576.1:p.Met1778Ile missense NM_001407648.1:c.5292G>A NP_001394577.1:p.Met1764Ile missense NM_001407649.1:c.5289G>A NP_001394578.1:p.Met1763Ile missense NM_001407652.1:c.5271G>A NP_001394581.1:p.Met1757Ile missense NM_001407653.1:c.5271G>A NP_001394582.1:p.Met1757Ile missense NM_001407654.1:c.5271G>A NP_001394583.1:p.Met1757Ile missense NM_001407655.1:c.5271G>A NP_001394584.1:p.Met1757Ile missense NM_001407656.1:c.5268G>A NP_001394585.1:p.Met1756Ile missense NM_001407657.1:c.5268G>A NP_001394586.1:p.Met1756Ile missense NM_001407658.1:c.5268G>A NP_001394587.1:p.Met1756Ile missense NM_001407659.1:c.5265G>A NP_001394588.1:p.Met1755Ile missense NM_001407660.1:c.5265G>A NP_001394589.1:p.Met1755Ile missense NM_001407661.1:c.5265G>A NP_001394590.1:p.Met1755Ile missense NM_001407662.1:c.5265G>A NP_001394591.1:p.Met1755Ile missense NM_001407663.1:c.5265G>A NP_001394592.1:p.Met1755Ile missense NM_001407664.1:c.5226G>A NP_001394593.1:p.Met1742Ile missense NM_001407665.1:c.5226G>A NP_001394594.1:p.Met1742Ile missense NM_001407666.1:c.5226G>A NP_001394595.1:p.Met1742Ile missense NM_001407667.1:c.5226G>A NP_001394596.1:p.Met1742Ile missense NM_001407668.1:c.5226G>A NP_001394597.1:p.Met1742Ile missense NM_001407669.1:c.5226G>A NP_001394598.1:p.Met1742Ile missense NM_001407670.1:c.5223G>A NP_001394599.1:p.Met1741Ile missense NM_001407671.1:c.5223G>A NP_001394600.1:p.Met1741Ile missense NM_001407672.1:c.5223G>A NP_001394601.1:p.Met1741Ile missense NM_001407673.1:c.5223G>A NP_001394602.1:p.Met1741Ile missense NM_001407674.1:c.5223G>A NP_001394603.1:p.Met1741Ile missense NM_001407675.1:c.5223G>A NP_001394604.1:p.Met1741Ile missense NM_001407676.1:c.5223G>A NP_001394605.1:p.Met1741Ile missense NM_001407677.1:c.5223G>A NP_001394606.1:p.Met1741Ile missense NM_001407678.1:c.5223G>A NP_001394607.1:p.Met1741Ile missense NM_001407679.1:c.5223G>A NP_001394608.1:p.Met1741Ile missense NM_001407680.1:c.5223G>A NP_001394609.1:p.Met1741Ile missense NM_001407681.1:c.5220G>A NP_001394610.1:p.Met1740Ile missense NM_001407682.1:c.5220G>A NP_001394611.1:p.Met1740Ile missense NM_001407683.1:c.5220G>A NP_001394612.1:p.Met1740Ile missense NM_001407685.1:c.5220G>A NP_001394614.1:p.Met1740Ile missense NM_001407686.1:c.5220G>A NP_001394615.1:p.Met1740Ile missense NM_001407687.1:c.5220G>A NP_001394616.1:p.Met1740Ile missense NM_001407688.1:c.5220G>A NP_001394617.1:p.Met1740Ile missense NM_001407689.1:c.5220G>A NP_001394618.1:p.Met1740Ile missense NM_001407690.1:c.5217G>A NP_001394619.1:p.Met1739Ile missense NM_001407691.1:c.5217G>A NP_001394620.1:p.Met1739Ile missense NM_001407692.1:c.5208G>A NP_001394621.1:p.Met1736Ile missense NM_001407694.1:c.5208G>A NP_001394623.1:p.Met1736Ile missense NM_001407695.1:c.5208G>A NP_001394624.1:p.Met1736Ile missense NM_001407696.1:c.5208G>A NP_001394625.1:p.Met1736Ile missense NM_001407697.1:c.5208G>A NP_001394626.1:p.Met1736Ile missense NM_001407698.1:c.5208G>A NP_001394627.1:p.Met1736Ile missense NM_001407724.1:c.5208G>A NP_001394653.1:p.Met1736Ile missense NM_001407725.1:c.5208G>A NP_001394654.1:p.Met1736Ile missense NM_001407726.1:c.5208G>A NP_001394655.1:p.Met1736Ile missense NM_001407727.1:c.5208G>A NP_001394656.1:p.Met1736Ile missense NM_001407728.1:c.5208G>A NP_001394657.1:p.Met1736Ile missense NM_001407729.1:c.5208G>A NP_001394658.1:p.Met1736Ile missense NM_001407730.1:c.5208G>A NP_001394659.1:p.Met1736Ile missense NM_001407731.1:c.5208G>A NP_001394660.1:p.Met1736Ile missense NM_001407732.1:c.5205G>A NP_001394661.1:p.Met1735Ile missense NM_001407733.1:c.5205G>A NP_001394662.1:p.Met1735Ile missense NM_001407734.1:c.5205G>A NP_001394663.1:p.Met1735Ile missense NM_001407735.1:c.5205G>A NP_001394664.1:p.Met1735Ile missense NM_001407736.1:c.5205G>A NP_001394665.1:p.Met1735Ile missense NM_001407737.1:c.5205G>A NP_001394666.1:p.Met1735Ile missense NM_001407738.1:c.5205G>A NP_001394667.1:p.Met1735Ile missense NM_001407739.1:c.5205G>A NP_001394668.1:p.Met1735Ile missense NM_001407740.1:c.5205G>A NP_001394669.1:p.Met1735Ile missense NM_001407741.1:c.5205G>A NP_001394670.1:p.Met1735Ile missense NM_001407742.1:c.5205G>A NP_001394671.1:p.Met1735Ile missense NM_001407743.1:c.5205G>A NP_001394672.1:p.Met1735Ile missense NM_001407744.1:c.5205G>A NP_001394673.1:p.Met1735Ile missense NM_001407745.1:c.5205G>A NP_001394674.1:p.Met1735Ile missense NM_001407746.1:c.5205G>A NP_001394675.1:p.Met1735Ile missense NM_001407747.1:c.5205G>A NP_001394676.1:p.Met1735Ile missense NM_001407748.1:c.5205G>A NP_001394677.1:p.Met1735Ile missense NM_001407749.1:c.5205G>A NP_001394678.1:p.Met1735Ile missense NM_001407750.1:c.5205G>A NP_001394679.1:p.Met1735Ile missense NM_001407751.1:c.5205G>A NP_001394680.1:p.Met1735Ile missense NM_001407752.1:c.5205G>A NP_001394681.1:p.Met1735Ile missense NM_001407838.1:c.5202G>A NP_001394767.1:p.Met1734Ile missense NM_001407839.1:c.5202G>A NP_001394768.1:p.Met1734Ile missense NM_001407841.1:c.5202G>A NP_001394770.1:p.Met1734Ile missense NM_001407842.1:c.5202G>A NP_001394771.1:p.Met1734Ile missense NM_001407843.1:c.5202G>A NP_001394772.1:p.Met1734Ile missense NM_001407844.1:c.5202G>A NP_001394773.1:p.Met1734Ile missense NM_001407845.1:c.5202G>A NP_001394774.1:p.Met1734Ile missense NM_001407846.1:c.5202G>A NP_001394775.1:p.Met1734Ile missense NM_001407847.1:c.5202G>A NP_001394776.1:p.Met1734Ile missense NM_001407848.1:c.5202G>A NP_001394777.1:p.Met1734Ile missense NM_001407849.1:c.5202G>A NP_001394778.1:p.Met1734Ile missense NM_001407850.1:c.5202G>A NP_001394779.1:p.Met1734Ile missense NM_001407851.1:c.5202G>A NP_001394780.1:p.Met1734Ile missense NM_001407852.1:c.5202G>A NP_001394781.1:p.Met1734Ile missense NM_001407853.1:c.5202G>A NP_001394782.1:p.Met1734Ile missense NM_001407862.1:c.5148G>A NP_001394791.1:p.Met1716Ile missense NM_001407863.1:c.5145G>A NP_001394792.1:p.Met1715Ile missense NM_001407874.1:c.5142G>A NP_001394803.1:p.Met1714Ile missense NM_001407875.1:c.5142G>A NP_001394804.1:p.Met1714Ile missense NM_001407879.1:c.5139G>A NP_001394808.1:p.Met1713Ile missense NM_001407881.1:c.5139G>A NP_001394810.1:p.Met1713Ile missense NM_001407882.1:c.5139G>A NP_001394811.1:p.Met1713Ile missense NM_001407884.1:c.5139G>A NP_001394813.1:p.Met1713Ile missense NM_001407885.1:c.5139G>A NP_001394814.1:p.Met1713Ile missense NM_001407886.1:c.5139G>A NP_001394815.1:p.Met1713Ile missense NM_001407887.1:c.5139G>A NP_001394816.1:p.Met1713Ile missense NM_001407889.1:c.5139G>A NP_001394818.1:p.Met1713Ile missense NM_001407894.1:c.5136G>A NP_001394823.1:p.Met1712Ile missense NM_001407895.1:c.5136G>A NP_001394824.1:p.Met1712Ile missense NM_001407896.1:c.5136G>A NP_001394825.1:p.Met1712Ile missense NM_001407897.1:c.5136G>A NP_001394826.1:p.Met1712Ile missense NM_001407898.1:c.5136G>A NP_001394827.1:p.Met1712Ile missense NM_001407899.1:c.5136G>A NP_001394828.1:p.Met1712Ile missense NM_001407900.1:c.5136G>A NP_001394829.1:p.Met1712Ile missense NM_001407902.1:c.5136G>A NP_001394831.1:p.Met1712Ile missense NM_001407904.1:c.5136G>A NP_001394833.1:p.Met1712Ile missense NM_001407906.1:c.5136G>A NP_001394835.1:p.Met1712Ile missense NM_001407907.1:c.5136G>A NP_001394836.1:p.Met1712Ile missense NM_001407908.1:c.5136G>A NP_001394837.1:p.Met1712Ile missense NM_001407909.1:c.5136G>A NP_001394838.1:p.Met1712Ile missense NM_001407910.1:c.5136G>A NP_001394839.1:p.Met1712Ile missense NM_001407915.1:c.5133G>A NP_001394844.1:p.Met1711Ile missense NM_001407916.1:c.5133G>A NP_001394845.1:p.Met1711Ile missense NM_001407917.1:c.5133G>A NP_001394846.1:p.Met1711Ile missense NM_001407918.1:c.5133G>A NP_001394847.1:p.Met1711Ile missense NM_001407920.1:c.5085G>A NP_001394849.1:p.Met1695Ile missense NM_001407921.1:c.5085G>A NP_001394850.1:p.Met1695Ile missense NM_001407922.1:c.5085G>A NP_001394851.1:p.Met1695Ile missense NM_001407923.1:c.5085G>A NP_001394852.1:p.Met1695Ile missense NM_001407924.1:c.5085G>A NP_001394853.1:p.Met1695Ile missense NM_001407925.1:c.5085G>A NP_001394854.1:p.Met1695Ile missense NM_001407926.1:c.5085G>A NP_001394855.1:p.Met1695Ile missense NM_001407927.1:c.5082G>A NP_001394856.1:p.Met1694Ile missense NM_001407928.1:c.5082G>A NP_001394857.1:p.Met1694Ile missense NM_001407929.1:c.5082G>A NP_001394858.1:p.Met1694Ile missense NM_001407930.1:c.5082G>A NP_001394859.1:p.Met1694Ile missense NM_001407931.1:c.5082G>A NP_001394860.1:p.Met1694Ile missense NM_001407932.1:c.5082G>A NP_001394861.1:p.Met1694Ile missense NM_001407933.1:c.5082G>A NP_001394862.1:p.Met1694Ile missense NM_001407934.1:c.5079G>A NP_001394863.1:p.Met1693Ile missense NM_001407935.1:c.5079G>A NP_001394864.1:p.Met1693Ile missense NM_001407936.1:c.5079G>A NP_001394865.1:p.Met1693Ile missense NM_001407946.1:c.5016G>A NP_001394875.1:p.Met1672Ile missense NM_001407947.1:c.5016G>A NP_001394876.1:p.Met1672Ile missense NM_001407948.1:c.5016G>A NP_001394877.1:p.Met1672Ile missense NM_001407949.1:c.5016G>A NP_001394878.1:p.Met1672Ile missense NM_001407950.1:c.5013G>A NP_001394879.1:p.Met1671Ile missense NM_001407951.1:c.5013G>A NP_001394880.1:p.Met1671Ile missense NM_001407952.1:c.5013G>A NP_001394881.1:p.Met1671Ile missense NM_001407953.1:c.5013G>A NP_001394882.1:p.Met1671Ile missense NM_001407954.1:c.5013G>A NP_001394883.1:p.Met1671Ile missense NM_001407955.1:c.5013G>A NP_001394884.1:p.Met1671Ile missense NM_001407956.1:c.5010G>A NP_001394885.1:p.Met1670Ile missense NM_001407957.1:c.5010G>A NP_001394886.1:p.Met1670Ile missense NM_001407958.1:c.5010G>A NP_001394887.1:p.Met1670Ile missense NM_001407959.1:c.4968G>A NP_001394888.1:p.Met1656Ile missense NM_001407960.1:c.4965G>A NP_001394889.1:p.Met1655Ile missense NM_001407962.1:c.4965G>A NP_001394891.1:p.Met1655Ile missense NM_001407963.1:c.4962G>A NP_001394892.1:p.Met1654Ile missense NM_001407964.1:c.4887G>A NP_001394893.1:p.Met1629Ile missense NM_001407965.1:c.4842G>A NP_001394894.1:p.Met1614Ile missense NM_001407966.1:c.4461G>A NP_001394895.1:p.Met1487Ile missense NM_001407967.1:c.4458G>A NP_001394896.1:p.Met1486Ile missense NM_001407968.1:c.2745G>A NP_001394897.1:p.Met915Ile missense NM_001407969.1:c.2742G>A NP_001394898.1:p.Met914Ile missense NM_001407970.1:c.2106G>A NP_001394899.1:p.Met702Ile missense NM_001407971.1:c.2106G>A NP_001394900.1:p.Met702Ile missense NM_001407972.1:c.2103G>A NP_001394901.1:p.Met701Ile missense NM_001407973.1:c.2040G>A NP_001394902.1:p.Met680Ile missense NM_001407974.1:c.2040G>A NP_001394903.1:p.Met680Ile missense NM_001407975.1:c.2040G>A NP_001394904.1:p.Met680Ile missense NM_001407976.1:c.2040G>A NP_001394905.1:p.Met680Ile missense NM_001407977.1:c.2040G>A NP_001394906.1:p.Met680Ile missense NM_001407978.1:c.2040G>A NP_001394907.1:p.Met680Ile missense NM_001407979.1:c.2037G>A NP_001394908.1:p.Met679Ile missense NM_001407980.1:c.2037G>A NP_001394909.1:p.Met679Ile missense NM_001407981.1:c.2037G>A NP_001394910.1:p.Met679Ile missense NM_001407982.1:c.2037G>A NP_001394911.1:p.Met679Ile missense NM_001407983.1:c.2037G>A NP_001394912.1:p.Met679Ile missense NM_001407984.1:c.2037G>A NP_001394913.1:p.Met679Ile missense NM_001407985.1:c.2037G>A NP_001394914.1:p.Met679Ile missense NM_001407986.1:c.2037G>A NP_001394915.1:p.Met679Ile missense NM_001407990.1:c.2037G>A NP_001394919.1:p.Met679Ile missense NM_001407991.1:c.2037G>A NP_001394920.1:p.Met679Ile missense NM_001407992.1:c.2037G>A NP_001394921.1:p.Met679Ile missense NM_001407993.1:c.2037G>A NP_001394922.1:p.Met679Ile missense NM_001408392.1:c.2034G>A NP_001395321.1:p.Met678Ile missense NM_001408396.1:c.2034G>A NP_001395325.1:p.Met678Ile missense NM_001408397.1:c.2034G>A NP_001395326.1:p.Met678Ile missense NM_001408398.1:c.2034G>A NP_001395327.1:p.Met678Ile missense NM_001408399.1:c.2034G>A NP_001395328.1:p.Met678Ile missense NM_001408400.1:c.2034G>A NP_001395329.1:p.Met678Ile missense NM_001408401.1:c.2034G>A NP_001395330.1:p.Met678Ile missense NM_001408402.1:c.2034G>A NP_001395331.1:p.Met678Ile missense NM_001408403.1:c.2034G>A NP_001395332.1:p.Met678Ile missense NM_001408404.1:c.2034G>A NP_001395333.1:p.Met678Ile missense NM_001408406.1:c.2031G>A NP_001395335.1:p.Met677Ile missense NM_001408407.1:c.2031G>A NP_001395336.1:p.Met677Ile missense NM_001408408.1:c.2031G>A NP_001395337.1:p.Met677Ile missense NM_001408409.1:c.2028G>A NP_001395338.1:p.Met676Ile missense NM_001408410.1:c.1965G>A NP_001395339.1:p.Met655Ile missense NM_001408411.1:c.1962G>A NP_001395340.1:p.Met654Ile missense NM_001408412.1:c.1959G>A NP_001395341.1:p.Met653Ile missense NM_001408413.1:c.1959G>A NP_001395342.1:p.Met653Ile missense NM_001408414.1:c.1959G>A NP_001395343.1:p.Met653Ile missense NM_001408415.1:c.1959G>A NP_001395344.1:p.Met653Ile missense NM_001408416.1:c.1959G>A NP_001395345.1:p.Met653Ile missense NM_001408418.1:c.1923G>A NP_001395347.1:p.Met641Ile missense NM_001408419.1:c.1923G>A NP_001395348.1:p.Met641Ile missense NM_001408420.1:c.1923G>A NP_001395349.1:p.Met641Ile missense NM_001408421.1:c.1920G>A NP_001395350.1:p.Met640Ile missense NM_001408422.1:c.1920G>A NP_001395351.1:p.Met640Ile missense NM_001408423.1:c.1920G>A NP_001395352.1:p.Met640Ile missense NM_001408424.1:c.1920G>A NP_001395353.1:p.Met640Ile missense NM_001408425.1:c.1917G>A NP_001395354.1:p.Met639Ile missense NM_001408426.1:c.1917G>A NP_001395355.1:p.Met639Ile missense NM_001408427.1:c.1917G>A NP_001395356.1:p.Met639Ile missense NM_001408428.1:c.1917G>A NP_001395357.1:p.Met639Ile missense NM_001408429.1:c.1917G>A NP_001395358.1:p.Met639Ile missense NM_001408430.1:c.1917G>A NP_001395359.1:p.Met639Ile missense NM_001408431.1:c.1917G>A NP_001395360.1:p.Met639Ile missense NM_001408432.1:c.1914G>A NP_001395361.1:p.Met638Ile missense NM_001408433.1:c.1914G>A NP_001395362.1:p.Met638Ile missense NM_001408434.1:c.1914G>A NP_001395363.1:p.Met638Ile missense NM_001408435.1:c.1914G>A NP_001395364.1:p.Met638Ile missense NM_001408436.1:c.1914G>A NP_001395365.1:p.Met638Ile missense NM_001408437.1:c.1914G>A NP_001395366.1:p.Met638Ile missense NM_001408438.1:c.1914G>A NP_001395367.1:p.Met638Ile missense NM_001408439.1:c.1914G>A NP_001395368.1:p.Met638Ile missense NM_001408440.1:c.1914G>A NP_001395369.1:p.Met638Ile missense NM_001408441.1:c.1914G>A NP_001395370.1:p.Met638Ile missense NM_001408442.1:c.1914G>A NP_001395371.1:p.Met638Ile missense NM_001408443.1:c.1914G>A NP_001395372.1:p.Met638Ile missense NM_001408444.1:c.1914G>A NP_001395373.1:p.Met638Ile missense NM_001408445.1:c.1911G>A NP_001395374.1:p.Met637Ile missense NM_001408446.1:c.1911G>A NP_001395375.1:p.Met637Ile missense NM_001408447.1:c.1911G>A NP_001395376.1:p.Met637Ile missense NM_001408448.1:c.1911G>A NP_001395377.1:p.Met637Ile missense NM_001408450.1:c.1911G>A NP_001395379.1:p.Met637Ile missense NM_001408451.1:c.1905G>A NP_001395380.1:p.Met635Ile missense NM_001408452.1:c.1899G>A NP_001395381.1:p.Met633Ile missense NM_001408453.1:c.1899G>A NP_001395382.1:p.Met633Ile missense NM_001408454.1:c.1899G>A NP_001395383.1:p.Met633Ile missense NM_001408455.1:c.1899G>A NP_001395384.1:p.Met633Ile missense NM_001408456.1:c.1899G>A NP_001395385.1:p.Met633Ile missense NM_001408457.1:c.1899G>A NP_001395386.1:p.Met633Ile missense NM_001408458.1:c.1896G>A NP_001395387.1:p.Met632Ile missense NM_001408459.1:c.1896G>A NP_001395388.1:p.Met632Ile missense NM_001408460.1:c.1896G>A NP_001395389.1:p.Met632Ile missense NM_001408461.1:c.1896G>A NP_001395390.1:p.Met632Ile missense NM_001408462.1:c.1896G>A NP_001395391.1:p.Met632Ile missense NM_001408463.1:c.1896G>A NP_001395392.1:p.Met632Ile missense NM_001408464.1:c.1896G>A NP_001395393.1:p.Met632Ile missense NM_001408465.1:c.1896G>A NP_001395394.1:p.Met632Ile missense NM_001408466.1:c.1896G>A NP_001395395.1:p.Met632Ile missense NM_001408467.1:c.1896G>A NP_001395396.1:p.Met632Ile missense NM_001408468.1:c.1893G>A NP_001395397.1:p.Met631Ile missense NM_001408469.1:c.1893G>A NP_001395398.1:p.Met631Ile missense NM_001408470.1:c.1893G>A NP_001395399.1:p.Met631Ile missense NM_001408474.1:c.1839G>A NP_001395403.1:p.Met613Ile missense NM_001408475.1:c.1836G>A NP_001395404.1:p.Met612Ile missense NM_001408476.1:c.1836G>A NP_001395405.1:p.Met612Ile missense NM_001408478.1:c.1830G>A NP_001395407.1:p.Met610Ile missense NM_001408479.1:c.1830G>A NP_001395408.1:p.Met610Ile missense NM_001408480.1:c.1830G>A NP_001395409.1:p.Met610Ile missense NM_001408481.1:c.1827G>A NP_001395410.1:p.Met609Ile missense NM_001408482.1:c.1827G>A NP_001395411.1:p.Met609Ile missense NM_001408483.1:c.1827G>A NP_001395412.1:p.Met609Ile missense NM_001408484.1:c.1827G>A NP_001395413.1:p.Met609Ile missense NM_001408485.1:c.1827G>A NP_001395414.1:p.Met609Ile missense NM_001408489.1:c.1827G>A NP_001395418.1:p.Met609Ile missense NM_001408490.1:c.1827G>A NP_001395419.1:p.Met609Ile missense NM_001408491.1:c.1827G>A NP_001395420.1:p.Met609Ile missense NM_001408492.1:c.1824G>A NP_001395421.1:p.Met608Ile missense NM_001408493.1:c.1824G>A NP_001395422.1:p.Met608Ile missense NM_001408494.1:c.1800G>A NP_001395423.1:p.Met600Ile missense NM_001408495.1:c.1794G>A NP_001395424.1:p.Met598Ile missense NM_001408496.1:c.1776G>A NP_001395425.1:p.Met592Ile missense NM_001408497.1:c.1776G>A NP_001395426.1:p.Met592Ile missense NM_001408498.1:c.1776G>A NP_001395427.1:p.Met592Ile missense NM_001408499.1:c.1776G>A NP_001395428.1:p.Met592Ile missense NM_001408500.1:c.1776G>A NP_001395429.1:p.Met592Ile missense NM_001408501.1:c.1776G>A NP_001395430.1:p.Met592Ile missense NM_001408502.1:c.1773G>A NP_001395431.1:p.Met591Ile missense NM_001408503.1:c.1773G>A NP_001395432.1:p.Met591Ile missense NM_001408504.1:c.1773G>A NP_001395433.1:p.Met591Ile missense NM_001408505.1:c.1770G>A NP_001395434.1:p.Met590Ile missense NM_001408506.1:c.1713G>A NP_001395435.1:p.Met571Ile missense NM_001408507.1:c.1710G>A NP_001395436.1:p.Met570Ile missense NM_001408508.1:c.1701G>A NP_001395437.1:p.Met567Ile missense NM_001408509.1:c.1698G>A NP_001395438.1:p.Met566Ile missense NM_001408510.1:c.1659G>A NP_001395439.1:p.Met553Ile missense NM_001408511.1:c.1656G>A NP_001395440.1:p.Met552Ile missense NM_001408512.1:c.1536G>A NP_001395441.1:p.Met512Ile missense NM_001408513.1:c.1509G>A NP_001395442.1:p.Met503Ile missense NM_001408514.1:c.1113G>A NP_001395443.1:p.Met371Ile missense NM_007297.4:c.5208G>A NP_009228.2:p.Met1736Ile missense NM_007298.4:c.2037G>A NP_009229.2:p.Met679Ile missense NM_007299.4:c.2021-1475G>A intron variant NM_007300.4:c.5412G>A NP_009231.2:p.Met1804Ile missense NM_007304.2:c.2037G>A NP_009235.2:p.Met679Ile missense NR_027676.2:n.5526G>A non-coding transcript variant NC_000017.11:g.43049178C>T NC_000017.10:g.41201195C>T NG_005905.2:g.168806G>A LRG_292:g.168806G>A LRG_292t1:c.5349G>A LRG_292p1:p.Met1783Ile - Protein change
- M1783I, M1804I, M1736I, M679I, M1629I, M1655I, M1656I, M1694I, M1695I, M1714I, M1734I, M1735I, M1756I, M1803I, M512I, M552I, M567I, M570I, M631I, M632I, M641I, M654I, M655I, M676I, M677I, M915I, M1614I, M1654I, M1715I, M1741I, M1742I, M1755I, M1763I, M1778I, M1805I, M598I, M600I, M608I, M638I, M639I, M640I, M653I, M680I, M1486I, M1670I, M1671I, M1693I, M1711I, M1716I, M1739I, M1740I, M1757I, M1780I, M371I, M566I, M609I, M633I, M635I, M637I, M678I, M701I, M702I, M1487I, M1672I, M1712I, M1713I, M1764I, M1779I, M1781I, M1782I, M503I, M553I, M571I, M590I, M591I, M592I, M610I, M612I, M613I, M914I
- Other names
- -
- Canonical SPDI
- NC_000017.11:43049177:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- functionally_normal Sequence Ontology [SO:0002219]
- The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5349G>A, a MISSENSE variant, produced a function score of 0.21, corresponding to a functional classification of FUNCTIONAL. 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) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
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 |
13029 | 14833 |
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. |
---|---|---|---|---|
Likely benign (1) |
criteria provided, single submitter
|
May 18, 2021 | RCV000130448.5 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 17, 2023 | RCV000587916.3 | |
Uncertain significance (2) |
criteria provided, single submitter
|
Sep 7, 2023 | RCV001073104.4 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Nov 9, 2023 | RCV001849935.7 |
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. |
|
---|---|---|---|---|---|
Uncertain significance
(Feb 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699248.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The BRCA1 c.5349G>A (p.Met1783Ile) causes a missense change involving the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome … (more)
Variant summary: The BRCA1 c.5349G>A (p.Met1783Ile) causes a missense change involving the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121,174 control chromosomes. The variant has been reported in one affected proband in the literature, along with a likely pathogenic variant that co-segregated with disease in the family, while the variant of interest was absent in two affected individuals (Ricevuto_2001). In functional studies, the variant showed comparable activity to wild-type BRCA1 (Lee_2010). One reputable clinical lab has classified the variant as a variant of uncertain significance. Taken together, this variant has been classified as a VUS-possibly benign. (less)
|
|
Uncertain significance
(Sep 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004212769.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
Uncertain significance
(Nov 09, 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: SCV002301370.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1783 of the BRCA1 protein (p.Met1783Ile). … (more)
This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1783 of the BRCA1 protein (p.Met1783Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 141796). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is not expected to disrupt BRCA1 function with a negative predictive value of 95%. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 20516115, 30209399, 30765603). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
|
|
Likely benign
(May 18, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000185312.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
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Uncertain significance
(Jan 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004219457.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
The frequency of this variant in the general population, 0.0000066 (1/152148 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the … (more)
The frequency of this variant in the general population, 0.0000066 (1/152148 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant was reported in a family affected with breast and ovarian cancer (PMID: 11410501 (2001)). Functional studies have shown the variant to have no protein folding defect, normal peptide binding activity and specificity, and normal transcriptional activity (PMID: 20516115 (2010), 24845084 (2014), 28781887 (2016), 29884841 (2019), 30209399 (2018)). Based on the available information, we are unable to determine the clinical significance of this variant. (less)
|
|
not provided
(-)
|
no classification provided
Method: in vitro
|
Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
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Brotman Baty Institute, University of Washington
Accession: SCV001238603.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
FUNCTIONAL:0.214041727107737
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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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
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A brief description of the result of this method for this variant. |
Submitter
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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
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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_normal
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001238603.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5349G>A, a MISSENSE variant, produced a function score of 0.21, corresponding to a functional classification of FUNCTIONAL. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5349G>A, a MISSENSE variant, produced a function score of 0.21, corresponding to a functional classification of FUNCTIONAL. 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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An integrative model for the comprehensive classification of BRCA1 and BRCA2 variants of uncertain clinical significance. | Iversen ES Jr | NPJ genomic medicine | 2022 | PMID: 35665744 |
Closing the gap: Systematic integration of multiplexed functional data resolves variants of uncertain significance in BRCA1, TP53, and PTEN. | Fayer S | American journal of human genetics | 2021 | PMID: 34793697 |
BRCA1 and BRCA2 Variation in Taiwanese General Population and the Cancer Cohort. | Chian J | Frontiers in molecular biosciences | 2021 | PMID: 34235180 |
Integration of functional assay data results provides strong evidence for classification of hundreds of BRCA1 variants of uncertain significance. | Lyra PCM Jr | Genetics in medicine : official journal of the American College of Medical Genetics | 2021 | PMID: 33087888 |
Classification of VUS and unclassified variants in BRCA1 BRCT repeats by molecular dynamics simulation. | Sinha S | Computational and structural biotechnology journal | 2020 | PMID: 32257056 |
Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots". | Dines JN | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31911673 |
Classification of variants of uncertain significance in BRCA1 and BRCA2 using personal and family history of cancer from individuals in a large hereditary cancer multigene panel testing cohort. | Li H | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31853058 |
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 |
Comprehensive annotation of BRCA1 and BRCA2 missense variants by functionally validated sequence-based computational prediction models. | Hart SN | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 29884841 |
Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance. | Woods NT | NPJ genomic medicine | 2016 | PMID: 28781887 |
Protein stability versus function: effects of destabilizing missense mutations on BRCA1 DNA repair activity. | Gaboriau DC | The Biochemical journal | 2015 | PMID: 25748678 |
Probing structure-function relationships in missense variants in the carboxy-terminal region of BRCA1. | Carvalho RS | PloS one | 2014 | PMID: 24845084 |
Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. | Lee MS | Cancer research | 2010 | PMID: 20516115 |
Diagnostic strategy for analytical scanning of BRCA1 gene by fluorescence-assisted mismatch analysis using large, bifluorescently labeled amplicons. | Ricevuto E | Clinical cancer research : an official journal of the American Association for Cancer Research | 2001 | PMID: 11410501 |
https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
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Text-mined citations for rs587782019 ...
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.