ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5512G>A (p.Val1838Met)
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(3); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5512G>A (p.Val1838Met)
Variation ID: 182173 Accession: VCV000182173.14
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43045758 (GRCh38) [ NCBI UCSC ] 17: 41197775 (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 May 29, 2016 Feb 14, 2024 Oct 15, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.5512G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Val1838Met missense NM_001407571.1:c.5299G>A NP_001394500.1:p.Val1767Met missense NM_001407581.1:c.5578G>A NP_001394510.1:p.Val1860Met missense NM_001407582.1:c.5578G>A NP_001394511.1:p.Val1860Met missense NM_001407583.1:c.5575G>A NP_001394512.1:p.Val1859Met missense NM_001407585.1:c.5575G>A NP_001394514.1:p.Val1859Met missense NM_001407587.1:c.5575G>A NP_001394516.1:p.Val1859Met missense NM_001407590.1:c.5572G>A NP_001394519.1:p.Val1858Met missense NM_001407591.1:c.5572G>A NP_001394520.1:p.Val1858Met missense NM_001407593.1:c.5512G>A NP_001394522.1:p.Val1838Met missense NM_001407594.1:c.5512G>A NP_001394523.1:p.Val1838Met missense NM_001407596.1:c.5512G>A NP_001394525.1:p.Val1838Met missense NM_001407597.1:c.5512G>A NP_001394526.1:p.Val1838Met missense NM_001407598.1:c.5512G>A NP_001394527.1:p.Val1838Met missense NM_001407602.1:c.5512G>A NP_001394531.1:p.Val1838Met missense NM_001407603.1:c.5512G>A NP_001394532.1:p.Val1838Met missense NM_001407605.1:c.5512G>A NP_001394534.1:p.Val1838Met missense NM_001407610.1:c.5509G>A NP_001394539.1:p.Val1837Met missense NM_001407611.1:c.5509G>A NP_001394540.1:p.Val1837Met missense NM_001407612.1:c.5509G>A NP_001394541.1:p.Val1837Met missense NM_001407613.1:c.5509G>A NP_001394542.1:p.Val1837Met missense NM_001407614.1:c.5509G>A NP_001394543.1:p.Val1837Met missense NM_001407615.1:c.5509G>A NP_001394544.1:p.Val1837Met missense NM_001407616.1:c.5509G>A NP_001394545.1:p.Val1837Met missense NM_001407617.1:c.5509G>A NP_001394546.1:p.Val1837Met missense NM_001407618.1:c.5509G>A NP_001394547.1:p.Val1837Met missense NM_001407619.1:c.5509G>A NP_001394548.1:p.Val1837Met missense NM_001407620.1:c.5509G>A NP_001394549.1:p.Val1837Met missense NM_001407621.1:c.5509G>A NP_001394550.1:p.Val1837Met missense NM_001407622.1:c.5509G>A NP_001394551.1:p.Val1837Met missense NM_001407623.1:c.5509G>A NP_001394552.1:p.Val1837Met missense NM_001407624.1:c.5509G>A NP_001394553.1:p.Val1837Met missense NM_001407625.1:c.5509G>A NP_001394554.1:p.Val1837Met missense NM_001407626.1:c.5509G>A NP_001394555.1:p.Val1837Met missense NM_001407627.1:c.5506G>A NP_001394556.1:p.Val1836Met missense NM_001407628.1:c.5506G>A NP_001394557.1:p.Val1836Met missense NM_001407629.1:c.5506G>A NP_001394558.1:p.Val1836Met missense NM_001407630.1:c.5506G>A NP_001394559.1:p.Val1836Met missense NM_001407631.1:c.5506G>A NP_001394560.1:p.Val1836Met missense NM_001407632.1:c.5506G>A NP_001394561.1:p.Val1836Met missense NM_001407633.1:c.5506G>A NP_001394562.1:p.Val1836Met missense NM_001407634.1:c.5506G>A NP_001394563.1:p.Val1836Met missense NM_001407635.1:c.5506G>A NP_001394564.1:p.Val1836Met missense NM_001407636.1:c.5506G>A NP_001394565.1:p.Val1836Met missense NM_001407637.1:c.5506G>A NP_001394566.1:p.Val1836Met missense NM_001407638.1:c.5506G>A NP_001394567.1:p.Val1836Met missense NM_001407639.1:c.5506G>A NP_001394568.1:p.Val1836Met missense NM_001407640.1:c.5506G>A NP_001394569.1:p.Val1836Met missense NM_001407641.1:c.5506G>A NP_001394570.1:p.Val1836Met missense NM_001407642.1:c.5506G>A NP_001394571.1:p.Val1836Met missense NM_001407644.1:c.5503G>A NP_001394573.1:p.Val1835Met missense NM_001407645.1:c.5503G>A NP_001394574.1:p.Val1835Met missense NM_001407646.1:c.5500G>A NP_001394575.1:p.Val1834Met missense NM_001407647.1:c.5497G>A NP_001394576.1:p.Val1833Met missense NM_001407648.1:c.5455G>A NP_001394577.1:p.Val1819Met missense NM_001407649.1:c.5452G>A NP_001394578.1:p.Val1818Met missense NM_001407652.1:c.5434G>A NP_001394581.1:p.Val1812Met missense NM_001407653.1:c.5434G>A NP_001394582.1:p.Val1812Met missense NM_001407654.1:c.5434G>A NP_001394583.1:p.Val1812Met missense NM_001407655.1:c.5434G>A NP_001394584.1:p.Val1812Met missense NM_001407656.1:c.5431G>A NP_001394585.1:p.Val1811Met missense NM_001407657.1:c.5431G>A NP_001394586.1:p.Val1811Met missense NM_001407658.1:c.5431G>A NP_001394587.1:p.Val1811Met missense NM_001407659.1:c.5428G>A NP_001394588.1:p.Val1810Met missense NM_001407660.1:c.5428G>A NP_001394589.1:p.Val1810Met missense NM_001407661.1:c.5428G>A NP_001394590.1:p.Val1810Met missense NM_001407662.1:c.5428G>A NP_001394591.1:p.Val1810Met missense NM_001407663.1:c.5428G>A NP_001394592.1:p.Val1810Met missense NM_001407664.1:c.5389G>A NP_001394593.1:p.Val1797Met missense NM_001407665.1:c.5389G>A NP_001394594.1:p.Val1797Met missense NM_001407666.1:c.5389G>A NP_001394595.1:p.Val1797Met missense NM_001407667.1:c.5389G>A NP_001394596.1:p.Val1797Met missense NM_001407668.1:c.5389G>A NP_001394597.1:p.Val1797Met missense NM_001407669.1:c.5389G>A NP_001394598.1:p.Val1797Met missense NM_001407670.1:c.5386G>A NP_001394599.1:p.Val1796Met missense NM_001407671.1:c.5386G>A NP_001394600.1:p.Val1796Met missense NM_001407672.1:c.5386G>A NP_001394601.1:p.Val1796Met missense NM_001407673.1:c.5386G>A NP_001394602.1:p.Val1796Met missense NM_001407674.1:c.5386G>A NP_001394603.1:p.Val1796Met missense NM_001407675.1:c.5386G>A NP_001394604.1:p.Val1796Met missense NM_001407676.1:c.5386G>A NP_001394605.1:p.Val1796Met missense NM_001407677.1:c.5386G>A NP_001394606.1:p.Val1796Met missense NM_001407678.1:c.5386G>A NP_001394607.1:p.Val1796Met missense NM_001407679.1:c.5386G>A NP_001394608.1:p.Val1796Met missense NM_001407680.1:c.5386G>A NP_001394609.1:p.Val1796Met missense NM_001407681.1:c.5383G>A NP_001394610.1:p.Val1795Met missense NM_001407682.1:c.5383G>A NP_001394611.1:p.Val1795Met missense NM_001407683.1:c.5383G>A NP_001394612.1:p.Val1795Met missense NM_001407684.1:c.5383G>A NP_001394613.1:p.Val1795Met missense NM_001407685.1:c.5383G>A NP_001394614.1:p.Val1795Met missense NM_001407686.1:c.5383G>A NP_001394615.1:p.Val1795Met missense NM_001407687.1:c.5383G>A NP_001394616.1:p.Val1795Met missense NM_001407688.1:c.5383G>A NP_001394617.1:p.Val1795Met missense NM_001407689.1:c.5383G>A NP_001394618.1:p.Val1795Met missense NM_001407690.1:c.5380G>A NP_001394619.1:p.Val1794Met missense NM_001407691.1:c.5380G>A NP_001394620.1:p.Val1794Met missense NM_001407692.1:c.5371G>A NP_001394621.1:p.Val1791Met missense NM_001407694.1:c.5371G>A NP_001394623.1:p.Val1791Met missense NM_001407695.1:c.5371G>A NP_001394624.1:p.Val1791Met missense NM_001407696.1:c.5371G>A NP_001394625.1:p.Val1791Met missense NM_001407697.1:c.5371G>A NP_001394626.1:p.Val1791Met missense NM_001407698.1:c.5371G>A NP_001394627.1:p.Val1791Met missense NM_001407724.1:c.5371G>A NP_001394653.1:p.Val1791Met missense NM_001407725.1:c.5371G>A NP_001394654.1:p.Val1791Met missense NM_001407726.1:c.5371G>A NP_001394655.1:p.Val1791Met missense NM_001407727.1:c.5371G>A NP_001394656.1:p.Val1791Met missense NM_001407728.1:c.5371G>A NP_001394657.1:p.Val1791Met missense NM_001407729.1:c.5371G>A NP_001394658.1:p.Val1791Met missense NM_001407730.1:c.5371G>A NP_001394659.1:p.Val1791Met missense NM_001407731.1:c.5371G>A NP_001394660.1:p.Val1791Met missense NM_001407732.1:c.5368G>A NP_001394661.1:p.Val1790Met missense NM_001407733.1:c.5368G>A NP_001394662.1:p.Val1790Met missense NM_001407734.1:c.5368G>A NP_001394663.1:p.Val1790Met missense NM_001407735.1:c.5368G>A NP_001394664.1:p.Val1790Met missense NM_001407736.1:c.5368G>A NP_001394665.1:p.Val1790Met missense NM_001407737.1:c.5368G>A NP_001394666.1:p.Val1790Met missense NM_001407738.1:c.5368G>A NP_001394667.1:p.Val1790Met missense NM_001407739.1:c.5368G>A NP_001394668.1:p.Val1790Met missense NM_001407740.1:c.5368G>A NP_001394669.1:p.Val1790Met missense NM_001407741.1:c.5368G>A NP_001394670.1:p.Val1790Met missense NM_001407742.1:c.5368G>A NP_001394671.1:p.Val1790Met missense NM_001407743.1:c.5368G>A NP_001394672.1:p.Val1790Met missense NM_001407744.1:c.5368G>A NP_001394673.1:p.Val1790Met missense NM_001407745.1:c.5368G>A NP_001394674.1:p.Val1790Met missense NM_001407746.1:c.5368G>A NP_001394675.1:p.Val1790Met missense NM_001407747.1:c.5368G>A NP_001394676.1:p.Val1790Met missense NM_001407748.1:c.5368G>A NP_001394677.1:p.Val1790Met missense NM_001407749.1:c.5368G>A NP_001394678.1:p.Val1790Met missense NM_001407750.1:c.5368G>A NP_001394679.1:p.Val1790Met missense NM_001407751.1:c.5368G>A NP_001394680.1:p.Val1790Met missense NM_001407752.1:c.5368G>A NP_001394681.1:p.Val1790Met missense NM_001407838.1:c.5365G>A NP_001394767.1:p.Val1789Met missense NM_001407839.1:c.5365G>A NP_001394768.1:p.Val1789Met missense NM_001407841.1:c.5365G>A NP_001394770.1:p.Val1789Met missense NM_001407842.1:c.5365G>A NP_001394771.1:p.Val1789Met missense NM_001407843.1:c.5365G>A NP_001394772.1:p.Val1789Met missense NM_001407844.1:c.5365G>A NP_001394773.1:p.Val1789Met missense NM_001407845.1:c.5365G>A NP_001394774.1:p.Val1789Met missense NM_001407846.1:c.5365G>A NP_001394775.1:p.Val1789Met missense NM_001407847.1:c.5365G>A NP_001394776.1:p.Val1789Met missense NM_001407848.1:c.5365G>A NP_001394777.1:p.Val1789Met missense NM_001407849.1:c.5365G>A NP_001394778.1:p.Val1789Met missense NM_001407850.1:c.5365G>A NP_001394779.1:p.Val1789Met missense NM_001407851.1:c.5365G>A NP_001394780.1:p.Val1789Met missense NM_001407852.1:c.5365G>A NP_001394781.1:p.Val1789Met missense NM_001407853.1:c.5365G>A NP_001394782.1:p.Val1789Met missense NM_001407854.1:c.*26G>A NM_001407858.1:c.*26G>A NM_001407859.1:c.*26G>A NM_001407860.1:c.*26G>A NM_001407861.1:c.*26G>A NM_001407862.1:c.5311G>A NP_001394791.1:p.Val1771Met missense NM_001407863.1:c.5308G>A NP_001394792.1:p.Val1770Met missense NM_001407874.1:c.5305G>A NP_001394803.1:p.Val1769Met missense NM_001407875.1:c.5305G>A NP_001394804.1:p.Val1769Met missense NM_001407879.1:c.5302G>A NP_001394808.1:p.Val1768Met missense NM_001407881.1:c.5302G>A NP_001394810.1:p.Val1768Met missense NM_001407882.1:c.5302G>A NP_001394811.1:p.Val1768Met missense NM_001407884.1:c.5302G>A NP_001394813.1:p.Val1768Met missense NM_001407885.1:c.5302G>A NP_001394814.1:p.Val1768Met missense NM_001407886.1:c.5302G>A NP_001394815.1:p.Val1768Met missense NM_001407887.1:c.5302G>A NP_001394816.1:p.Val1768Met missense NM_001407889.1:c.5302G>A NP_001394818.1:p.Val1768Met missense NM_001407894.1:c.5299G>A NP_001394823.1:p.Val1767Met missense NM_001407895.1:c.5299G>A NP_001394824.1:p.Val1767Met missense NM_001407896.1:c.5299G>A NP_001394825.1:p.Val1767Met missense NM_001407897.1:c.5299G>A NP_001394826.1:p.Val1767Met missense NM_001407898.1:c.5299G>A NP_001394827.1:p.Val1767Met missense NM_001407899.1:c.5299G>A NP_001394828.1:p.Val1767Met missense NM_001407900.1:c.5299G>A NP_001394829.1:p.Val1767Met missense NM_001407902.1:c.5299G>A NP_001394831.1:p.Val1767Met missense NM_001407904.1:c.5299G>A NP_001394833.1:p.Val1767Met missense NM_001407906.1:c.5299G>A NP_001394835.1:p.Val1767Met missense NM_001407907.1:c.5299G>A NP_001394836.1:p.Val1767Met missense NM_001407908.1:c.5299G>A NP_001394837.1:p.Val1767Met missense NM_001407909.1:c.5299G>A NP_001394838.1:p.Val1767Met missense NM_001407910.1:c.5299G>A NP_001394839.1:p.Val1767Met missense NM_001407915.1:c.5296G>A NP_001394844.1:p.Val1766Met missense NM_001407916.1:c.5296G>A NP_001394845.1:p.Val1766Met missense NM_001407917.1:c.5296G>A NP_001394846.1:p.Val1766Met missense NM_001407918.1:c.5296G>A NP_001394847.1:p.Val1766Met missense NM_001407919.1:c.5260G>A NP_001394848.1:p.Val1754Met missense NM_001407920.1:c.5248G>A NP_001394849.1:p.Val1750Met missense NM_001407921.1:c.5248G>A NP_001394850.1:p.Val1750Met missense NM_001407922.1:c.5248G>A NP_001394851.1:p.Val1750Met missense NM_001407923.1:c.5248G>A NP_001394852.1:p.Val1750Met missense NM_001407924.1:c.5248G>A NP_001394853.1:p.Val1750Met missense NM_001407925.1:c.5248G>A NP_001394854.1:p.Val1750Met missense NM_001407926.1:c.5248G>A NP_001394855.1:p.Val1750Met missense NM_001407927.1:c.5245G>A NP_001394856.1:p.Val1749Met missense NM_001407928.1:c.5245G>A NP_001394857.1:p.Val1749Met missense NM_001407929.1:c.5245G>A NP_001394858.1:p.Val1749Met missense NM_001407930.1:c.5245G>A NP_001394859.1:p.Val1749Met missense NM_001407931.1:c.5245G>A NP_001394860.1:p.Val1749Met missense NM_001407932.1:c.5245G>A NP_001394861.1:p.Val1749Met missense NM_001407933.1:c.5245G>A NP_001394862.1:p.Val1749Met missense NM_001407934.1:c.5242G>A NP_001394863.1:p.Val1748Met missense NM_001407935.1:c.5242G>A NP_001394864.1:p.Val1748Met missense NM_001407936.1:c.5242G>A NP_001394865.1:p.Val1748Met missense NM_001407937.1:c.*26G>A NM_001407938.1:c.*26G>A NM_001407939.1:c.*26G>A NM_001407940.1:c.*26G>A NM_001407941.1:c.*26G>A NM_001407942.1:c.*26G>A NM_001407943.1:c.*26G>A NM_001407944.1:c.*26G>A NM_001407945.1:c.*26G>A NM_001407946.1:c.5179G>A NP_001394875.1:p.Val1727Met missense NM_001407947.1:c.5179G>A NP_001394876.1:p.Val1727Met missense NM_001407948.1:c.5179G>A NP_001394877.1:p.Val1727Met missense NM_001407949.1:c.5179G>A NP_001394878.1:p.Val1727Met missense NM_001407950.1:c.5176G>A NP_001394879.1:p.Val1726Met missense NM_001407951.1:c.5176G>A NP_001394880.1:p.Val1726Met missense NM_001407952.1:c.5176G>A NP_001394881.1:p.Val1726Met missense NM_001407953.1:c.5176G>A NP_001394882.1:p.Val1726Met missense NM_001407954.1:c.5176G>A NP_001394883.1:p.Val1726Met missense NM_001407955.1:c.5176G>A NP_001394884.1:p.Val1726Met missense NM_001407956.1:c.5173G>A NP_001394885.1:p.Val1725Met missense NM_001407957.1:c.5173G>A NP_001394886.1:p.Val1725Met missense NM_001407958.1:c.5173G>A NP_001394887.1:p.Val1725Met missense NM_001407959.1:c.5131G>A NP_001394888.1:p.Val1711Met missense NM_001407960.1:c.5128G>A NP_001394889.1:p.Val1710Met missense NM_001407962.1:c.5128G>A NP_001394891.1:p.Val1710Met missense NM_001407963.1:c.5125G>A NP_001394892.1:p.Val1709Met missense NM_001407964.1:c.5050G>A NP_001394893.1:p.Val1684Met missense NM_001407965.1:c.5005G>A NP_001394894.1:p.Val1669Met missense NM_001407966.1:c.4624G>A NP_001394895.1:p.Val1542Met missense NM_001407967.1:c.4621G>A NP_001394896.1:p.Val1541Met missense NM_001407968.1:c.2908G>A NP_001394897.1:p.Val970Met missense NM_001407969.1:c.2905G>A NP_001394898.1:p.Val969Met missense NM_001407970.1:c.2269G>A NP_001394899.1:p.Val757Met missense NM_001407971.1:c.2269G>A NP_001394900.1:p.Val757Met missense NM_001407972.1:c.2266G>A NP_001394901.1:p.Val756Met missense NM_001407973.1:c.2203G>A NP_001394902.1:p.Val735Met missense NM_001407974.1:c.2203G>A NP_001394903.1:p.Val735Met missense NM_001407975.1:c.2203G>A NP_001394904.1:p.Val735Met missense NM_001407976.1:c.2203G>A NP_001394905.1:p.Val735Met missense NM_001407977.1:c.2203G>A NP_001394906.1:p.Val735Met missense NM_001407978.1:c.2203G>A NP_001394907.1:p.Val735Met missense NM_001407979.1:c.2200G>A NP_001394908.1:p.Val734Met missense NM_001407980.1:c.2200G>A NP_001394909.1:p.Val734Met missense NM_001407981.1:c.2200G>A NP_001394910.1:p.Val734Met missense NM_001407982.1:c.2200G>A NP_001394911.1:p.Val734Met missense NM_001407983.1:c.2200G>A NP_001394912.1:p.Val734Met missense NM_001407984.1:c.2200G>A NP_001394913.1:p.Val734Met missense NM_001407985.1:c.2200G>A NP_001394914.1:p.Val734Met missense NM_001407986.1:c.2200G>A NP_001394915.1:p.Val734Met missense NM_001407990.1:c.2200G>A NP_001394919.1:p.Val734Met missense NM_001407991.1:c.2200G>A NP_001394920.1:p.Val734Met missense NM_001407992.1:c.2200G>A NP_001394921.1:p.Val734Met missense NM_001407993.1:c.2200G>A NP_001394922.1:p.Val734Met missense NM_001408392.1:c.2197G>A NP_001395321.1:p.Val733Met missense NM_001408396.1:c.2197G>A NP_001395325.1:p.Val733Met missense NM_001408397.1:c.2197G>A NP_001395326.1:p.Val733Met missense NM_001408398.1:c.2197G>A NP_001395327.1:p.Val733Met missense NM_001408399.1:c.2197G>A NP_001395328.1:p.Val733Met missense NM_001408400.1:c.2197G>A NP_001395329.1:p.Val733Met missense NM_001408401.1:c.2197G>A NP_001395330.1:p.Val733Met missense NM_001408402.1:c.2197G>A NP_001395331.1:p.Val733Met missense NM_001408403.1:c.2197G>A NP_001395332.1:p.Val733Met missense NM_001408404.1:c.2197G>A NP_001395333.1:p.Val733Met missense NM_001408406.1:c.2194G>A NP_001395335.1:p.Val732Met missense NM_001408407.1:c.2194G>A NP_001395336.1:p.Val732Met missense NM_001408408.1:c.2194G>A NP_001395337.1:p.Val732Met missense NM_001408409.1:c.2191G>A NP_001395338.1:p.Val731Met missense NM_001408410.1:c.2128G>A NP_001395339.1:p.Val710Met missense NM_001408411.1:c.2125G>A NP_001395340.1:p.Val709Met missense NM_001408412.1:c.2122G>A NP_001395341.1:p.Val708Met missense NM_001408413.1:c.2122G>A NP_001395342.1:p.Val708Met missense NM_001408414.1:c.2122G>A NP_001395343.1:p.Val708Met missense NM_001408415.1:c.2122G>A NP_001395344.1:p.Val708Met missense NM_001408416.1:c.2122G>A NP_001395345.1:p.Val708Met missense NM_001408418.1:c.2086G>A NP_001395347.1:p.Val696Met missense NM_001408419.1:c.2086G>A NP_001395348.1:p.Val696Met missense NM_001408420.1:c.2086G>A NP_001395349.1:p.Val696Met missense NM_001408421.1:c.2083G>A NP_001395350.1:p.Val695Met missense NM_001408422.1:c.2083G>A NP_001395351.1:p.Val695Met missense NM_001408423.1:c.2083G>A NP_001395352.1:p.Val695Met missense NM_001408424.1:c.2083G>A NP_001395353.1:p.Val695Met missense NM_001408425.1:c.2080G>A NP_001395354.1:p.Val694Met missense NM_001408426.1:c.2080G>A NP_001395355.1:p.Val694Met missense NM_001408427.1:c.2080G>A NP_001395356.1:p.Val694Met missense NM_001408428.1:c.2080G>A NP_001395357.1:p.Val694Met missense NM_001408429.1:c.2080G>A NP_001395358.1:p.Val694Met missense NM_001408430.1:c.2080G>A NP_001395359.1:p.Val694Met missense NM_001408431.1:c.2080G>A NP_001395360.1:p.Val694Met missense NM_001408432.1:c.2077G>A NP_001395361.1:p.Val693Met missense NM_001408433.1:c.2077G>A NP_001395362.1:p.Val693Met missense NM_001408434.1:c.2077G>A NP_001395363.1:p.Val693Met missense NM_001408435.1:c.2077G>A NP_001395364.1:p.Val693Met missense NM_001408436.1:c.2077G>A NP_001395365.1:p.Val693Met missense NM_001408437.1:c.2077G>A NP_001395366.1:p.Val693Met missense NM_001408438.1:c.2077G>A NP_001395367.1:p.Val693Met missense NM_001408439.1:c.2077G>A NP_001395368.1:p.Val693Met missense NM_001408440.1:c.2077G>A NP_001395369.1:p.Val693Met missense NM_001408441.1:c.2077G>A NP_001395370.1:p.Val693Met missense NM_001408442.1:c.2077G>A NP_001395371.1:p.Val693Met missense NM_001408443.1:c.2077G>A NP_001395372.1:p.Val693Met missense NM_001408444.1:c.2077G>A NP_001395373.1:p.Val693Met missense NM_001408445.1:c.2074G>A NP_001395374.1:p.Val692Met missense NM_001408446.1:c.2074G>A NP_001395375.1:p.Val692Met missense NM_001408447.1:c.2074G>A NP_001395376.1:p.Val692Met missense NM_001408448.1:c.2074G>A NP_001395377.1:p.Val692Met missense NM_001408450.1:c.2074G>A NP_001395379.1:p.Val692Met missense NM_001408451.1:c.2068G>A NP_001395380.1:p.Val690Met missense NM_001408452.1:c.2062G>A NP_001395381.1:p.Val688Met missense NM_001408453.1:c.2062G>A NP_001395382.1:p.Val688Met missense NM_001408454.1:c.2062G>A NP_001395383.1:p.Val688Met missense NM_001408455.1:c.2062G>A NP_001395384.1:p.Val688Met missense NM_001408456.1:c.2062G>A NP_001395385.1:p.Val688Met missense NM_001408457.1:c.2062G>A NP_001395386.1:p.Val688Met missense NM_001408458.1:c.2059G>A NP_001395387.1:p.Val687Met missense NM_001408459.1:c.2059G>A NP_001395388.1:p.Val687Met missense NM_001408460.1:c.2059G>A NP_001395389.1:p.Val687Met missense NM_001408461.1:c.2059G>A NP_001395390.1:p.Val687Met missense NM_001408462.1:c.2059G>A NP_001395391.1:p.Val687Met missense NM_001408463.1:c.2059G>A NP_001395392.1:p.Val687Met missense NM_001408464.1:c.2059G>A NP_001395393.1:p.Val687Met missense NM_001408465.1:c.2059G>A NP_001395394.1:p.Val687Met missense NM_001408466.1:c.2059G>A NP_001395395.1:p.Val687Met missense NM_001408467.1:c.2059G>A NP_001395396.1:p.Val687Met missense NM_001408468.1:c.2056G>A NP_001395397.1:p.Val686Met missense NM_001408469.1:c.2056G>A NP_001395398.1:p.Val686Met missense NM_001408470.1:c.2056G>A NP_001395399.1:p.Val686Met missense NM_001408472.1:c.*26G>A NM_001408473.1:c.*26G>A NM_001408474.1:c.2002G>A NP_001395403.1:p.Val668Met missense NM_001408475.1:c.1999G>A NP_001395404.1:p.Val667Met missense NM_001408476.1:c.1999G>A NP_001395405.1:p.Val667Met missense NM_001408478.1:c.1993G>A NP_001395407.1:p.Val665Met missense NM_001408479.1:c.1993G>A NP_001395408.1:p.Val665Met missense NM_001408480.1:c.1993G>A NP_001395409.1:p.Val665Met missense NM_001408481.1:c.1990G>A NP_001395410.1:p.Val664Met missense NM_001408482.1:c.1990G>A NP_001395411.1:p.Val664Met missense NM_001408483.1:c.1990G>A NP_001395412.1:p.Val664Met missense NM_001408484.1:c.1990G>A NP_001395413.1:p.Val664Met missense NM_001408485.1:c.1990G>A NP_001395414.1:p.Val664Met missense NM_001408489.1:c.1990G>A NP_001395418.1:p.Val664Met missense NM_001408490.1:c.1990G>A NP_001395419.1:p.Val664Met missense NM_001408491.1:c.1990G>A NP_001395420.1:p.Val664Met missense NM_001408492.1:c.1987G>A NP_001395421.1:p.Val663Met missense NM_001408493.1:c.1987G>A NP_001395422.1:p.Val663Met missense NM_001408494.1:c.1963G>A NP_001395423.1:p.Val655Met missense NM_001408495.1:c.1957G>A NP_001395424.1:p.Val653Met missense NM_001408496.1:c.1939G>A NP_001395425.1:p.Val647Met missense NM_001408497.1:c.1939G>A NP_001395426.1:p.Val647Met missense NM_001408498.1:c.1939G>A NP_001395427.1:p.Val647Met missense NM_001408499.1:c.1939G>A NP_001395428.1:p.Val647Met missense NM_001408500.1:c.1939G>A NP_001395429.1:p.Val647Met missense NM_001408501.1:c.1939G>A NP_001395430.1:p.Val647Met missense NM_001408502.1:c.1936G>A NP_001395431.1:p.Val646Met missense NM_001408503.1:c.1936G>A NP_001395432.1:p.Val646Met missense NM_001408504.1:c.1936G>A NP_001395433.1:p.Val646Met missense NM_001408505.1:c.1933G>A NP_001395434.1:p.Val645Met missense NM_001408506.1:c.1876G>A NP_001395435.1:p.Val626Met missense NM_001408507.1:c.1873G>A NP_001395436.1:p.Val625Met missense NM_001408508.1:c.1864G>A NP_001395437.1:p.Val622Met missense NM_001408509.1:c.1861G>A NP_001395438.1:p.Val621Met missense NM_001408510.1:c.1822G>A NP_001395439.1:p.Val608Met missense NM_001408511.1:c.1819G>A NP_001395440.1:p.Val607Met missense NM_001408512.1:c.1699G>A NP_001395441.1:p.Val567Met missense NM_001408513.1:c.1672G>A NP_001395442.1:p.Val558Met missense NM_001408514.1:c.1276G>A NP_001395443.1:p.Val426Met missense NM_007297.4:c.5371G>A NP_009228.2:p.Val1791Met missense NM_007298.4:c.2200G>A NP_009229.2:p.Val734Met missense NM_007299.4:c.*26G>A 3 prime UTR NM_007300.4:c.5575G>A NP_009231.2:p.Val1859Met missense NM_007304.2:c.2200G>A NP_009235.2:p.Val734Met missense NR_027676.2:n.5689G>A non-coding transcript variant NC_000017.11:g.43045758C>T NC_000017.10:g.41197775C>T NG_005905.2:g.172226G>A LRG_292:g.172226G>A LRG_292t1:c.5512G>A LRG_292p1:p.Val1838Met - Protein change
- V1838M, V1859M, V734M, V1791M, V1669M, V1710M, V1754M, V1769M, V1835M, V1837M, V567M, V607M, V608M, V622M, V647M, V667M, V690M, V695M, V732M, V970M, V1541M, V1684M, V1711M, V1726M, V1750M, V1770M, V1790M, V1796M, V1797M, V1819M, V1834M, V1836M, V626M, V645M, V653M, V655M, V663M, V664M, V668M, V686M, V688M, V692M, V694M, V710M, V969M, V1542M, V1709M, V1725M, V1727M, V1748M, V1768M, V1789M, V1794M, V1811M, V1818M, V621M, V687M, V693M, V708M, V731M, V733M, V735M, V757M, V1749M, V1766M, V1767M, V1771M, V1795M, V1810M, V1812M, V1833M, V1858M, V1860M, V426M, V558M, V625M, V646M, V665M, V696M, V709M, V756M
- Other names
- p.V1838M:GTG>ATG
- Canonical SPDI
- NC_000017.11:43045757: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.5512G>A, a MISSENSE variant, produced a function score of -0.55, 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.
Trans-Omics for Precision Medicine (TOPMed) 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 |
12795 | 14565 |
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. |
---|---|---|---|---|
Uncertain significance (1) |
criteria provided, single submitter
|
Feb 25, 2014 | RCV000160014.3 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Oct 15, 2023 | RCV000689723.7 | |
not provided (1) |
no classification provided
|
- | RCV001078020.2 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Jul 15, 2021 | RCV001181283.6 |
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 25, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000210230.10
First in ClinVar: Feb 24, 2015 Last updated: May 29, 2016 |
Comment:
This variant is denoted BRCA1 c.5512G>A at the cDNA level, p.Val1838Met (V1838M) at the protein level, and results in the change of a Valine to … (more)
This variant is denoted BRCA1 c.5512G>A at the cDNA level, p.Val1838Met (V1838M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Val1838Met was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating 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 and is unlikely to affect protein integrity. BRCA1 Val1838Met occurs at a position that is well conserved across species and is located in the BRCT2 domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether BRCA1 Val1838Met is pathogenic or benign. We consider it to be a variant of uncertain significance. (less)
|
|
Likely benign
(Jul 15, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002648678.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, … (more)
This alteration is classified as likely benign based on a combination of the following: 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)
Number of individuals with the variant: 1
|
|
Uncertain significance
(Oct 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000817388.4
First in ClinVar: Oct 10, 2018 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 1838 of the BRCA1 protein (p.Val1838Met). … (more)
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1838 of the BRCA1 protein (p.Val1838Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 182173). 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. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). This variant disrupts the p.Val1838 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18375895, 20516115, 21990134, 27272900). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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)
|
|
Uncertain significance
(Aug 09, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV001346394.2
First in ClinVar: Jun 22, 2020 Last updated: Jan 12, 2022 |
Comment:
This missense variant replaces valine with methionine at codon 1838 of the BRCA1 protein. Computational prediction tools and conservation analyses suggest that this variant may … (more)
This missense variant replaces valine with methionine at codon 1838 of the BRCA1 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. This variant has been reported to be functional in a haploid cell proliferation assay (PMID: 30209399). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. Different variants affecting the same position (p.Val1838Glu and p.Val1838Gly) are considered to be disease-causing (ClinVar variation ID: 55611, 254643), suggesting that valine at this position is important for protein structure and function. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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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: SCV001244043.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
FUNCTIONAL:-0.553037930952023
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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: SCV001244043.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5512G>A, a MISSENSE variant, produced a function score of -0.55, corresponding to a functional classification of FUNCTIONAL. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5512G>A, a MISSENSE variant, produced a function score of -0.55, 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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Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
Functional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making. | Thouvenot P | PLoS genetics | 2016 | PMID: 27272900 |
A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS). | Lindor NM | Human mutation | 2012 | PMID: 21990134 |
LOVD v.2.0: the next generation in gene variant databases. | Fokkema IF | Human mutation | 2011 | PMID: 21520333 |
Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. | Lee MS | Cancer research | 2010 | PMID: 20516115 |
Clinical classification of BRCA1 and BRCA2 DNA sequence variants: the value of cytokeratin profiles and evolutionary analysis--a report from the kConFab Investigators. | Spurdle AB | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2008 | PMID: 18375895 |
https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
Text-mined citations for rs730881501 ...
HelpRecord last updated Mar 30, 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.