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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been reported not to substantially affect BRCA1 protein function (PMID: 30209399). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 844324). This variant is present in population databases (rs771606902, ExAC 0.01%). This sequence change replaces methionine with valine at codon 1827 of the BRCA1 protein (p.Met1827Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5479A>G (p.Met1827Val)
Germline
Classification
Help
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.
(5)
Help
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.
Conflicting classifications of pathogenicity
Uncertain significance(3); Likely benign(1)
Uncertain significance(3); Likely benign(1)
5
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.5479A>G (p.Met1827Val)
Variation ID: 844324 Accession: VCV000844324.14
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43045791 (GRCh38) [ NCBI UCSC ] 17: 41197808 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 15, 2020 Nov 24, 2024 Apr 12, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5479A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Met1827Val missense NM_001407571.1:c.5266A>G NP_001394500.1:p.Met1756Val missense NM_001407581.1:c.5545A>G NP_001394510.1:p.Met1849Val missense NM_001407582.1:c.5545A>G NP_001394511.1:p.Met1849Val missense NM_001407583.1:c.5542A>G NP_001394512.1:p.Met1848Val missense NM_001407585.1:c.5542A>G NP_001394514.1:p.Met1848Val missense NM_001407587.1:c.5542A>G NP_001394516.1:p.Met1848Val missense NM_001407590.1:c.5539A>G NP_001394519.1:p.Met1847Val missense NM_001407591.1:c.5539A>G NP_001394520.1:p.Met1847Val missense NM_001407593.1:c.5479A>G NP_001394522.1:p.Met1827Val missense NM_001407594.1:c.5479A>G NP_001394523.1:p.Met1827Val missense NM_001407596.1:c.5479A>G NP_001394525.1:p.Met1827Val missense NM_001407597.1:c.5479A>G NP_001394526.1:p.Met1827Val missense NM_001407598.1:c.5479A>G NP_001394527.1:p.Met1827Val missense NM_001407602.1:c.5479A>G NP_001394531.1:p.Met1827Val missense NM_001407603.1:c.5479A>G NP_001394532.1:p.Met1827Val missense NM_001407605.1:c.5479A>G NP_001394534.1:p.Met1827Val missense NM_001407610.1:c.5476A>G NP_001394539.1:p.Met1826Val missense NM_001407611.1:c.5476A>G NP_001394540.1:p.Met1826Val missense NM_001407612.1:c.5476A>G NP_001394541.1:p.Met1826Val missense NM_001407613.1:c.5476A>G NP_001394542.1:p.Met1826Val missense NM_001407614.1:c.5476A>G NP_001394543.1:p.Met1826Val missense NM_001407615.1:c.5476A>G NP_001394544.1:p.Met1826Val missense NM_001407616.1:c.5476A>G NP_001394545.1:p.Met1826Val missense NM_001407617.1:c.5476A>G NP_001394546.1:p.Met1826Val missense NM_001407618.1:c.5476A>G NP_001394547.1:p.Met1826Val missense NM_001407619.1:c.5476A>G NP_001394548.1:p.Met1826Val missense NM_001407620.1:c.5476A>G NP_001394549.1:p.Met1826Val missense NM_001407621.1:c.5476A>G NP_001394550.1:p.Met1826Val missense NM_001407622.1:c.5476A>G NP_001394551.1:p.Met1826Val missense NM_001407623.1:c.5476A>G NP_001394552.1:p.Met1826Val missense NM_001407624.1:c.5476A>G NP_001394553.1:p.Met1826Val missense NM_001407625.1:c.5476A>G NP_001394554.1:p.Met1826Val missense NM_001407626.1:c.5476A>G NP_001394555.1:p.Met1826Val missense NM_001407627.1:c.5473A>G NP_001394556.1:p.Met1825Val missense NM_001407628.1:c.5473A>G NP_001394557.1:p.Met1825Val missense NM_001407629.1:c.5473A>G NP_001394558.1:p.Met1825Val missense NM_001407630.1:c.5473A>G NP_001394559.1:p.Met1825Val missense NM_001407631.1:c.5473A>G NP_001394560.1:p.Met1825Val missense NM_001407632.1:c.5473A>G NP_001394561.1:p.Met1825Val missense NM_001407633.1:c.5473A>G NP_001394562.1:p.Met1825Val missense NM_001407634.1:c.5473A>G NP_001394563.1:p.Met1825Val missense NM_001407635.1:c.5473A>G NP_001394564.1:p.Met1825Val missense NM_001407636.1:c.5473A>G NP_001394565.1:p.Met1825Val missense NM_001407637.1:c.5473A>G NP_001394566.1:p.Met1825Val missense NM_001407638.1:c.5473A>G NP_001394567.1:p.Met1825Val missense NM_001407639.1:c.5473A>G NP_001394568.1:p.Met1825Val missense NM_001407640.1:c.5473A>G NP_001394569.1:p.Met1825Val missense NM_001407641.1:c.5473A>G NP_001394570.1:p.Met1825Val missense NM_001407642.1:c.5473A>G NP_001394571.1:p.Met1825Val missense NM_001407644.1:c.5470A>G NP_001394573.1:p.Met1824Val missense NM_001407645.1:c.5470A>G NP_001394574.1:p.Met1824Val missense NM_001407646.1:c.5467A>G NP_001394575.1:p.Met1823Val missense NM_001407647.1:c.5464A>G NP_001394576.1:p.Met1822Val missense NM_001407648.1:c.5422A>G NP_001394577.1:p.Met1808Val missense NM_001407649.1:c.5419A>G NP_001394578.1:p.Met1807Val missense NM_001407652.1:c.5401A>G NP_001394581.1:p.Met1801Val missense NM_001407653.1:c.5401A>G NP_001394582.1:p.Met1801Val missense NM_001407654.1:c.5401A>G NP_001394583.1:p.Met1801Val missense NM_001407655.1:c.5401A>G NP_001394584.1:p.Met1801Val missense NM_001407656.1:c.5398A>G NP_001394585.1:p.Met1800Val missense NM_001407657.1:c.5398A>G NP_001394586.1:p.Met1800Val missense NM_001407658.1:c.5398A>G NP_001394587.1:p.Met1800Val missense NM_001407659.1:c.5395A>G NP_001394588.1:p.Met1799Val missense NM_001407660.1:c.5395A>G NP_001394589.1:p.Met1799Val missense NM_001407661.1:c.5395A>G NP_001394590.1:p.Met1799Val missense NM_001407662.1:c.5395A>G NP_001394591.1:p.Met1799Val missense NM_001407663.1:c.5395A>G NP_001394592.1:p.Met1799Val missense NM_001407664.1:c.5356A>G NP_001394593.1:p.Met1786Val missense NM_001407665.1:c.5356A>G NP_001394594.1:p.Met1786Val missense NM_001407666.1:c.5356A>G NP_001394595.1:p.Met1786Val missense NM_001407667.1:c.5356A>G NP_001394596.1:p.Met1786Val missense NM_001407668.1:c.5356A>G NP_001394597.1:p.Met1786Val missense NM_001407669.1:c.5356A>G NP_001394598.1:p.Met1786Val missense NM_001407670.1:c.5353A>G NP_001394599.1:p.Met1785Val missense NM_001407671.1:c.5353A>G NP_001394600.1:p.Met1785Val missense NM_001407672.1:c.5353A>G NP_001394601.1:p.Met1785Val missense NM_001407673.1:c.5353A>G NP_001394602.1:p.Met1785Val missense NM_001407674.1:c.5353A>G NP_001394603.1:p.Met1785Val missense NM_001407675.1:c.5353A>G NP_001394604.1:p.Met1785Val missense NM_001407676.1:c.5353A>G NP_001394605.1:p.Met1785Val missense NM_001407677.1:c.5353A>G NP_001394606.1:p.Met1785Val missense NM_001407678.1:c.5353A>G NP_001394607.1:p.Met1785Val missense NM_001407679.1:c.5353A>G NP_001394608.1:p.Met1785Val missense NM_001407680.1:c.5353A>G NP_001394609.1:p.Met1785Val missense NM_001407681.1:c.5350A>G NP_001394610.1:p.Met1784Val missense NM_001407682.1:c.5350A>G NP_001394611.1:p.Met1784Val missense NM_001407683.1:c.5350A>G NP_001394612.1:p.Met1784Val missense NM_001407684.1:c.5350A>G NP_001394613.1:p.Met1784Val missense NM_001407685.1:c.5350A>G NP_001394614.1:p.Met1784Val missense NM_001407686.1:c.5350A>G NP_001394615.1:p.Met1784Val missense NM_001407687.1:c.5350A>G NP_001394616.1:p.Met1784Val missense NM_001407688.1:c.5350A>G NP_001394617.1:p.Met1784Val missense NM_001407689.1:c.5350A>G NP_001394618.1:p.Met1784Val missense NM_001407690.1:c.5347A>G NP_001394619.1:p.Met1783Val missense NM_001407691.1:c.5347A>G NP_001394620.1:p.Met1783Val missense NM_001407692.1:c.5338A>G NP_001394621.1:p.Met1780Val missense NM_001407694.1:c.5338A>G NP_001394623.1:p.Met1780Val missense NM_001407695.1:c.5338A>G NP_001394624.1:p.Met1780Val missense NM_001407696.1:c.5338A>G NP_001394625.1:p.Met1780Val missense NM_001407697.1:c.5338A>G NP_001394626.1:p.Met1780Val missense NM_001407698.1:c.5338A>G NP_001394627.1:p.Met1780Val missense NM_001407724.1:c.5338A>G NP_001394653.1:p.Met1780Val missense NM_001407725.1:c.5338A>G NP_001394654.1:p.Met1780Val missense NM_001407726.1:c.5338A>G NP_001394655.1:p.Met1780Val missense NM_001407727.1:c.5338A>G NP_001394656.1:p.Met1780Val missense NM_001407728.1:c.5338A>G NP_001394657.1:p.Met1780Val missense NM_001407729.1:c.5338A>G NP_001394658.1:p.Met1780Val missense NM_001407730.1:c.5338A>G NP_001394659.1:p.Met1780Val missense NM_001407731.1:c.5338A>G NP_001394660.1:p.Met1780Val missense NM_001407732.1:c.5335A>G NP_001394661.1:p.Met1779Val missense NM_001407733.1:c.5335A>G NP_001394662.1:p.Met1779Val missense NM_001407734.1:c.5335A>G NP_001394663.1:p.Met1779Val missense NM_001407735.1:c.5335A>G NP_001394664.1:p.Met1779Val missense NM_001407736.1:c.5335A>G NP_001394665.1:p.Met1779Val missense NM_001407737.1:c.5335A>G NP_001394666.1:p.Met1779Val missense NM_001407738.1:c.5335A>G NP_001394667.1:p.Met1779Val missense NM_001407739.1:c.5335A>G NP_001394668.1:p.Met1779Val missense NM_001407740.1:c.5335A>G NP_001394669.1:p.Met1779Val missense NM_001407741.1:c.5335A>G NP_001394670.1:p.Met1779Val missense NM_001407742.1:c.5335A>G NP_001394671.1:p.Met1779Val missense NM_001407743.1:c.5335A>G NP_001394672.1:p.Met1779Val missense NM_001407744.1:c.5335A>G NP_001394673.1:p.Met1779Val missense NM_001407745.1:c.5335A>G NP_001394674.1:p.Met1779Val missense NM_001407746.1:c.5335A>G NP_001394675.1:p.Met1779Val missense NM_001407747.1:c.5335A>G NP_001394676.1:p.Met1779Val missense NM_001407748.1:c.5335A>G NP_001394677.1:p.Met1779Val missense NM_001407749.1:c.5335A>G NP_001394678.1:p.Met1779Val missense NM_001407750.1:c.5335A>G NP_001394679.1:p.Met1779Val missense NM_001407751.1:c.5335A>G NP_001394680.1:p.Met1779Val missense NM_001407752.1:c.5335A>G NP_001394681.1:p.Met1779Val missense NM_001407838.1:c.5332A>G NP_001394767.1:p.Met1778Val missense NM_001407839.1:c.5332A>G NP_001394768.1:p.Met1778Val missense NM_001407841.1:c.5332A>G NP_001394770.1:p.Met1778Val missense NM_001407842.1:c.5332A>G NP_001394771.1:p.Met1778Val missense NM_001407843.1:c.5332A>G NP_001394772.1:p.Met1778Val missense NM_001407844.1:c.5332A>G NP_001394773.1:p.Met1778Val missense NM_001407845.1:c.5332A>G NP_001394774.1:p.Met1778Val missense NM_001407846.1:c.5332A>G NP_001394775.1:p.Met1778Val missense NM_001407847.1:c.5332A>G NP_001394776.1:p.Met1778Val missense NM_001407848.1:c.5332A>G NP_001394777.1:p.Met1778Val missense NM_001407849.1:c.5332A>G NP_001394778.1:p.Met1778Val missense NM_001407850.1:c.5332A>G NP_001394779.1:p.Met1778Val missense NM_001407851.1:c.5332A>G NP_001394780.1:p.Met1778Val missense NM_001407852.1:c.5332A>G NP_001394781.1:p.Met1778Val missense NM_001407853.1:c.5332A>G NP_001394782.1:p.Met1778Val missense NM_001407854.1:c.5405A>G NP_001394783.1:p.Asp1802Gly missense NM_001407858.1:c.5402A>G NP_001394787.1:p.Asp1801Gly missense NM_001407859.1:c.5402A>G NP_001394788.1:p.Asp1801Gly missense NM_001407860.1:c.5402A>G NP_001394789.1:p.Asp1801Gly missense NM_001407861.1:c.5399A>G NP_001394790.1:p.Asp1800Gly missense NM_001407862.1:c.5278A>G NP_001394791.1:p.Met1760Val missense NM_001407863.1:c.5275A>G NP_001394792.1:p.Met1759Val missense NM_001407874.1:c.5272A>G NP_001394803.1:p.Met1758Val missense NM_001407875.1:c.5272A>G NP_001394804.1:p.Met1758Val missense NM_001407879.1:c.5269A>G NP_001394808.1:p.Met1757Val missense NM_001407881.1:c.5269A>G NP_001394810.1:p.Met1757Val missense NM_001407882.1:c.5269A>G NP_001394811.1:p.Met1757Val missense NM_001407884.1:c.5269A>G NP_001394813.1:p.Met1757Val missense NM_001407885.1:c.5269A>G NP_001394814.1:p.Met1757Val missense NM_001407886.1:c.5269A>G NP_001394815.1:p.Met1757Val missense NM_001407887.1:c.5269A>G NP_001394816.1:p.Met1757Val missense NM_001407889.1:c.5269A>G NP_001394818.1:p.Met1757Val missense NM_001407894.1:c.5266A>G NP_001394823.1:p.Met1756Val missense NM_001407895.1:c.5266A>G NP_001394824.1:p.Met1756Val missense NM_001407896.1:c.5266A>G NP_001394825.1:p.Met1756Val missense NM_001407897.1:c.5266A>G NP_001394826.1:p.Met1756Val missense NM_001407898.1:c.5266A>G NP_001394827.1:p.Met1756Val missense NM_001407899.1:c.5266A>G NP_001394828.1:p.Met1756Val missense NM_001407900.1:c.5266A>G NP_001394829.1:p.Met1756Val missense NM_001407902.1:c.5266A>G NP_001394831.1:p.Met1756Val missense NM_001407904.1:c.5266A>G NP_001394833.1:p.Met1756Val missense NM_001407906.1:c.5266A>G NP_001394835.1:p.Met1756Val missense NM_001407907.1:c.5266A>G NP_001394836.1:p.Met1756Val missense NM_001407908.1:c.5266A>G NP_001394837.1:p.Met1756Val missense NM_001407909.1:c.5266A>G NP_001394838.1:p.Met1756Val missense NM_001407910.1:c.5266A>G NP_001394839.1:p.Met1756Val missense NM_001407915.1:c.5263A>G NP_001394844.1:p.Met1755Val missense NM_001407916.1:c.5263A>G NP_001394845.1:p.Met1755Val missense NM_001407917.1:c.5263A>G NP_001394846.1:p.Met1755Val missense NM_001407918.1:c.5263A>G NP_001394847.1:p.Met1755Val missense NM_001407919.1:c.5227A>G NP_001394848.1:p.Met1743Val missense NM_001407920.1:c.5215A>G NP_001394849.1:p.Met1739Val missense NM_001407921.1:c.5215A>G NP_001394850.1:p.Met1739Val missense NM_001407922.1:c.5215A>G NP_001394851.1:p.Met1739Val missense NM_001407923.1:c.5215A>G NP_001394852.1:p.Met1739Val missense NM_001407924.1:c.5215A>G NP_001394853.1:p.Met1739Val missense NM_001407925.1:c.5215A>G NP_001394854.1:p.Met1739Val missense NM_001407926.1:c.5215A>G NP_001394855.1:p.Met1739Val missense NM_001407927.1:c.5212A>G NP_001394856.1:p.Met1738Val missense NM_001407928.1:c.5212A>G NP_001394857.1:p.Met1738Val missense NM_001407929.1:c.5212A>G NP_001394858.1:p.Met1738Val missense NM_001407930.1:c.5212A>G NP_001394859.1:p.Met1738Val missense NM_001407931.1:c.5212A>G NP_001394860.1:p.Met1738Val missense NM_001407932.1:c.5212A>G NP_001394861.1:p.Met1738Val missense NM_001407933.1:c.5212A>G NP_001394862.1:p.Met1738Val missense NM_001407934.1:c.5209A>G NP_001394863.1:p.Met1737Val missense NM_001407935.1:c.5209A>G NP_001394864.1:p.Met1737Val missense NM_001407936.1:c.5209A>G NP_001394865.1:p.Met1737Val missense NM_001407937.1:c.5282A>G NP_001394866.1:p.Asp1761Gly missense NM_001407938.1:c.5282A>G NP_001394867.1:p.Asp1761Gly missense NM_001407939.1:c.5279A>G NP_001394868.1:p.Asp1760Gly missense NM_001407940.1:c.5279A>G NP_001394869.1:p.Asp1760Gly missense NM_001407941.1:c.5276A>G NP_001394870.1:p.Asp1759Gly missense NM_001407942.1:c.5264A>G NP_001394871.1:p.Asp1755Gly missense NM_001407943.1:c.5261A>G NP_001394872.1:p.Asp1754Gly missense NM_001407944.1:c.5261A>G NP_001394873.1:p.Asp1754Gly missense NM_001407945.1:c.5261A>G NP_001394874.1:p.Asp1754Gly missense NM_001407946.1:c.5146A>G NP_001394875.1:p.Met1716Val missense NM_001407947.1:c.5146A>G NP_001394876.1:p.Met1716Val missense NM_001407948.1:c.5146A>G NP_001394877.1:p.Met1716Val missense NM_001407949.1:c.5146A>G NP_001394878.1:p.Met1716Val missense NM_001407950.1:c.5143A>G NP_001394879.1:p.Met1715Val missense NM_001407951.1:c.5143A>G NP_001394880.1:p.Met1715Val missense NM_001407952.1:c.5143A>G NP_001394881.1:p.Met1715Val missense NM_001407953.1:c.5143A>G NP_001394882.1:p.Met1715Val missense NM_001407954.1:c.5143A>G NP_001394883.1:p.Met1715Val missense NM_001407955.1:c.5143A>G NP_001394884.1:p.Met1715Val missense NM_001407956.1:c.5140A>G NP_001394885.1:p.Met1714Val missense NM_001407957.1:c.5140A>G NP_001394886.1:p.Met1714Val missense NM_001407958.1:c.5140A>G NP_001394887.1:p.Met1714Val missense NM_001407959.1:c.5098A>G NP_001394888.1:p.Met1700Val missense NM_001407960.1:c.5095A>G NP_001394889.1:p.Met1699Val missense NM_001407962.1:c.5095A>G NP_001394891.1:p.Met1699Val missense NM_001407963.1:c.5092A>G NP_001394892.1:p.Met1698Val missense NM_001407964.1:c.5017A>G NP_001394893.1:p.Met1673Val missense NM_001407965.1:c.4972A>G NP_001394894.1:p.Met1658Val missense NM_001407966.1:c.4591A>G NP_001394895.1:p.Met1531Val missense NM_001407967.1:c.4588A>G NP_001394896.1:p.Met1530Val missense NM_001407968.1:c.2875A>G NP_001394897.1:p.Met959Val missense NM_001407969.1:c.2872A>G NP_001394898.1:p.Met958Val missense NM_001407970.1:c.2236A>G NP_001394899.1:p.Met746Val missense NM_001407971.1:c.2236A>G NP_001394900.1:p.Met746Val missense NM_001407972.1:c.2233A>G NP_001394901.1:p.Met745Val missense NM_001407973.1:c.2170A>G NP_001394902.1:p.Met724Val missense NM_001407974.1:c.2170A>G NP_001394903.1:p.Met724Val missense NM_001407975.1:c.2170A>G NP_001394904.1:p.Met724Val missense NM_001407976.1:c.2170A>G NP_001394905.1:p.Met724Val missense NM_001407977.1:c.2170A>G NP_001394906.1:p.Met724Val missense NM_001407978.1:c.2170A>G NP_001394907.1:p.Met724Val missense NM_001407979.1:c.2167A>G NP_001394908.1:p.Met723Val missense NM_001407980.1:c.2167A>G NP_001394909.1:p.Met723Val missense NM_001407981.1:c.2167A>G NP_001394910.1:p.Met723Val missense NM_001407982.1:c.2167A>G NP_001394911.1:p.Met723Val missense NM_001407983.1:c.2167A>G NP_001394912.1:p.Met723Val missense NM_001407984.1:c.2167A>G NP_001394913.1:p.Met723Val missense NM_001407985.1:c.2167A>G NP_001394914.1:p.Met723Val missense NM_001407986.1:c.2167A>G NP_001394915.1:p.Met723Val missense NM_001407990.1:c.2167A>G NP_001394919.1:p.Met723Val missense NM_001407991.1:c.2167A>G NP_001394920.1:p.Met723Val missense NM_001407992.1:c.2167A>G NP_001394921.1:p.Met723Val missense NM_001407993.1:c.2167A>G NP_001394922.1:p.Met723Val missense NM_001408392.1:c.2164A>G NP_001395321.1:p.Met722Val missense NM_001408396.1:c.2164A>G NP_001395325.1:p.Met722Val missense NM_001408397.1:c.2164A>G NP_001395326.1:p.Met722Val missense NM_001408398.1:c.2164A>G NP_001395327.1:p.Met722Val missense NM_001408399.1:c.2164A>G NP_001395328.1:p.Met722Val missense NM_001408400.1:c.2164A>G NP_001395329.1:p.Met722Val missense NM_001408401.1:c.2164A>G NP_001395330.1:p.Met722Val missense NM_001408402.1:c.2164A>G NP_001395331.1:p.Met722Val missense NM_001408403.1:c.2164A>G NP_001395332.1:p.Met722Val missense NM_001408404.1:c.2164A>G NP_001395333.1:p.Met722Val missense NM_001408406.1:c.2161A>G NP_001395335.1:p.Met721Val missense NM_001408407.1:c.2161A>G NP_001395336.1:p.Met721Val missense NM_001408408.1:c.2161A>G NP_001395337.1:p.Met721Val missense NM_001408409.1:c.2158A>G NP_001395338.1:p.Met720Val missense NM_001408410.1:c.2095A>G NP_001395339.1:p.Met699Val missense NM_001408411.1:c.2092A>G NP_001395340.1:p.Met698Val missense NM_001408412.1:c.2089A>G NP_001395341.1:p.Met697Val missense NM_001408413.1:c.2089A>G NP_001395342.1:p.Met697Val missense NM_001408414.1:c.2089A>G NP_001395343.1:p.Met697Val missense NM_001408415.1:c.2089A>G NP_001395344.1:p.Met697Val missense NM_001408416.1:c.2089A>G NP_001395345.1:p.Met697Val missense NM_001408418.1:c.2053A>G NP_001395347.1:p.Met685Val missense NM_001408419.1:c.2053A>G NP_001395348.1:p.Met685Val missense NM_001408420.1:c.2053A>G NP_001395349.1:p.Met685Val missense NM_001408421.1:c.2050A>G NP_001395350.1:p.Met684Val missense NM_001408422.1:c.2050A>G NP_001395351.1:p.Met684Val missense NM_001408423.1:c.2050A>G NP_001395352.1:p.Met684Val missense NM_001408424.1:c.2050A>G NP_001395353.1:p.Met684Val missense NM_001408425.1:c.2047A>G NP_001395354.1:p.Met683Val missense NM_001408426.1:c.2047A>G NP_001395355.1:p.Met683Val missense NM_001408427.1:c.2047A>G NP_001395356.1:p.Met683Val missense NM_001408428.1:c.2047A>G NP_001395357.1:p.Met683Val missense NM_001408429.1:c.2047A>G NP_001395358.1:p.Met683Val missense NM_001408430.1:c.2047A>G NP_001395359.1:p.Met683Val missense NM_001408431.1:c.2047A>G NP_001395360.1:p.Met683Val missense NM_001408432.1:c.2044A>G NP_001395361.1:p.Met682Val missense NM_001408433.1:c.2044A>G NP_001395362.1:p.Met682Val missense NM_001408434.1:c.2044A>G NP_001395363.1:p.Met682Val missense NM_001408435.1:c.2044A>G NP_001395364.1:p.Met682Val missense NM_001408436.1:c.2044A>G NP_001395365.1:p.Met682Val missense NM_001408437.1:c.2044A>G NP_001395366.1:p.Met682Val missense NM_001408438.1:c.2044A>G NP_001395367.1:p.Met682Val missense NM_001408439.1:c.2044A>G NP_001395368.1:p.Met682Val missense NM_001408440.1:c.2044A>G NP_001395369.1:p.Met682Val missense NM_001408441.1:c.2044A>G NP_001395370.1:p.Met682Val missense NM_001408442.1:c.2044A>G NP_001395371.1:p.Met682Val missense NM_001408443.1:c.2044A>G NP_001395372.1:p.Met682Val missense NM_001408444.1:c.2044A>G NP_001395373.1:p.Met682Val missense NM_001408445.1:c.2041A>G NP_001395374.1:p.Met681Val missense NM_001408446.1:c.2041A>G NP_001395375.1:p.Met681Val missense NM_001408447.1:c.2041A>G NP_001395376.1:p.Met681Val missense NM_001408448.1:c.2041A>G NP_001395377.1:p.Met681Val missense NM_001408450.1:c.2041A>G NP_001395379.1:p.Met681Val missense NM_001408451.1:c.2035A>G NP_001395380.1:p.Met679Val missense NM_001408452.1:c.2029A>G NP_001395381.1:p.Met677Val missense NM_001408453.1:c.2029A>G NP_001395382.1:p.Met677Val missense NM_001408454.1:c.2029A>G NP_001395383.1:p.Met677Val missense NM_001408455.1:c.2029A>G NP_001395384.1:p.Met677Val missense NM_001408456.1:c.2029A>G NP_001395385.1:p.Met677Val missense NM_001408457.1:c.2029A>G NP_001395386.1:p.Met677Val missense NM_001408458.1:c.2026A>G NP_001395387.1:p.Met676Val missense NM_001408459.1:c.2026A>G NP_001395388.1:p.Met676Val missense NM_001408460.1:c.2026A>G NP_001395389.1:p.Met676Val missense NM_001408461.1:c.2026A>G NP_001395390.1:p.Met676Val missense NM_001408462.1:c.2026A>G NP_001395391.1:p.Met676Val missense NM_001408463.1:c.2026A>G NP_001395392.1:p.Met676Val missense NM_001408464.1:c.2026A>G NP_001395393.1:p.Met676Val missense NM_001408465.1:c.2026A>G NP_001395394.1:p.Met676Val missense NM_001408466.1:c.2026A>G NP_001395395.1:p.Met676Val missense NM_001408467.1:c.2026A>G NP_001395396.1:p.Met676Val missense NM_001408468.1:c.2023A>G NP_001395397.1:p.Met675Val missense NM_001408469.1:c.2023A>G NP_001395398.1:p.Met675Val missense NM_001408470.1:c.2023A>G NP_001395399.1:p.Met675Val missense NM_001408472.1:c.2093A>G NP_001395401.1:p.Asp698Gly missense NM_001408473.1:c.2090A>G NP_001395402.1:p.Asp697Gly missense NM_001408474.1:c.1969A>G NP_001395403.1:p.Met657Val missense NM_001408475.1:c.1966A>G NP_001395404.1:p.Met656Val missense NM_001408476.1:c.1966A>G NP_001395405.1:p.Met656Val missense NM_001408478.1:c.1960A>G NP_001395407.1:p.Met654Val missense NM_001408479.1:c.1960A>G NP_001395408.1:p.Met654Val missense NM_001408480.1:c.1960A>G NP_001395409.1:p.Met654Val missense NM_001408481.1:c.1957A>G NP_001395410.1:p.Met653Val missense NM_001408482.1:c.1957A>G NP_001395411.1:p.Met653Val missense NM_001408483.1:c.1957A>G NP_001395412.1:p.Met653Val missense NM_001408484.1:c.1957A>G NP_001395413.1:p.Met653Val missense NM_001408485.1:c.1957A>G NP_001395414.1:p.Met653Val missense NM_001408489.1:c.1957A>G NP_001395418.1:p.Met653Val missense NM_001408490.1:c.1957A>G NP_001395419.1:p.Met653Val missense NM_001408491.1:c.1957A>G NP_001395420.1:p.Met653Val missense NM_001408492.1:c.1954A>G NP_001395421.1:p.Met652Val missense NM_001408493.1:c.1954A>G NP_001395422.1:p.Met652Val missense NM_001408494.1:c.1930A>G NP_001395423.1:p.Met644Val missense NM_001408495.1:c.1924A>G NP_001395424.1:p.Met642Val missense NM_001408496.1:c.1906A>G NP_001395425.1:p.Met636Val missense NM_001408497.1:c.1906A>G NP_001395426.1:p.Met636Val missense NM_001408498.1:c.1906A>G NP_001395427.1:p.Met636Val missense NM_001408499.1:c.1906A>G NP_001395428.1:p.Met636Val missense NM_001408500.1:c.1906A>G NP_001395429.1:p.Met636Val missense NM_001408501.1:c.1906A>G NP_001395430.1:p.Met636Val missense NM_001408502.1:c.1903A>G NP_001395431.1:p.Met635Val missense NM_001408503.1:c.1903A>G NP_001395432.1:p.Met635Val missense NM_001408504.1:c.1903A>G NP_001395433.1:p.Met635Val missense NM_001408505.1:c.1900A>G NP_001395434.1:p.Met634Val missense NM_001408506.1:c.1843A>G NP_001395435.1:p.Met615Val missense NM_001408507.1:c.1840A>G NP_001395436.1:p.Met614Val missense NM_001408508.1:c.1831A>G NP_001395437.1:p.Met611Val missense NM_001408509.1:c.1828A>G NP_001395438.1:p.Met610Val missense NM_001408510.1:c.1789A>G NP_001395439.1:p.Met597Val missense NM_001408511.1:c.1786A>G NP_001395440.1:p.Met596Val missense NM_001408512.1:c.1666A>G NP_001395441.1:p.Met556Val missense NM_001408513.1:c.1639A>G NP_001395442.1:p.Met547Val missense NM_001408514.1:c.1243A>G NP_001395443.1:p.Met415Val missense NM_007297.4:c.5338A>G NP_009228.2:p.Met1780Val missense NM_007298.4:c.2167A>G NP_009229.2:p.Met723Val missense NM_007299.4:c.2093A>G NP_009230.2:p.Asp698Gly missense NM_007300.4:c.5542A>G NP_009231.2:p.Met1848Val missense NM_007304.2:c.2167A>G NP_009235.2:p.Met723Val missense NR_027676.2:n.5656A>G non-coding transcript variant NC_000017.11:g.43045791T>C NC_000017.10:g.41197808T>C NG_005905.2:g.172193A>G LRG_292:g.172193A>G LRG_292t1:c.5479A>G LRG_292p1:p.Met1827Val - Protein change
- M1848V, M1780V, M1827V, M723V, D698G, D1754G, D1755G, D1759G, D1761G, M1658V, M1700V, M1755V, M1778V, M1779V, M1785V, M1823V, M556V, M611V, M634V, M675V, M677V, M699V, M724V, M746V, D1802G, M1531V, M1673V, M1699V, M1715V, M1737V, M1738V, M1757V, M1759V, M1783V, M1786V, M1807V, M1822V, M1826V, M547V, M597V, M610V, M614V, M642V, M679V, M681V, M683V, M685V, M697V, M720V, M958V, M959V, D1760G, D1801G, M1698V, M1739V, M1756V, M1784V, M1801V, M1808V, M1825V, M1849V, M415V, M615V, M652V, M653V, M656V, M657V, M676V, M698V, M722V, D1800G, D697G, M1530V, M1714V, M1716V, M1743V, M1758V, M1760V, M1799V, M1800V, M1824V, M1847V, M596V, M635V, M636V, M644V, M654V, M682V, M684V, M721V, M745V
- Other names
- -
- Canonical SPDI
- NC_000017.11:43045790:T:C
-
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.5479A>G, a MISSENSE variant, produced a function score of -0.28, 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), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13050 | 14856 | |
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
|
Jun 7, 2020 | RCV001047143.9 | |
| Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Apr 12, 2024 | RCV001072218.5 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Mar 2, 2020 | RCV002348376.2 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Jun 07, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001211080.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 20, 2024 |
Comment:
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 … (more)
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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been reported not to substantially affect BRCA1 protein function (PMID: 30209399). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 844324). This variant is present in population databases (rs771606902, ExAC 0.01%). This sequence change replaces methionine with valine at codon 1827 of the BRCA1 protein (p.Met1827Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. (less)
|
|
|
Uncertain significance
(Mar 02, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002648179.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.M1827V variant (also known as c.5479A>G), located in coding exon 22 of the BRCA1 gene, results from an A to G substitution at nucleotide … (more)
The p.M1827V variant (also known as c.5479A>G), located in coding exon 22 of the BRCA1 gene, results from an A to G substitution at nucleotide position 5479. The methionine at codon 1827 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
|
Uncertain significance
(Jan 02, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV005058284.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
|
|
|
Likely Benign
(Apr 12, 2024)
|
criteria provided, single submitter
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine
Accession: SCV005402715.1
First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024 |
Comment:
Each variant was annotated with functional scores from MAVE data which was translated into functional evidence codes. All other evidence codes and combining criteria were … (more)
Each variant was annotated with functional scores from MAVE data which was translated into functional evidence codes. All other evidence codes and combining criteria were adhered to as closely as possible based on the ClinGen VCEP (Variant Curation Expert Panel) gene-specific recommendations. See Supplemental Figure 34 of final paper (Supp Fig. 28 in preprint: doi:10.1101/2024.04.11.24305690) for a table to see which lines of evidence we did not have data for. The ClinGen VCEPs are highly regarded as the gold-standard for gene-specific variant curation and are developed after extensive evaluation of the evidence by clinical and scientific experts for the particular gene to classify genomic variants on a spectrum from pathogenic to benign using the 2015 ACMG/AMP Variant Interpretation Guidelines as a backbone (PMID: 25741868). Reclassification of these VUS variants from gnomAD or All of Us focused only on variants originally prescribed as VUS in ClinVar. To ensure reproducibility, transparency, and increased throughput, all the procedures for annotating variants and assigning evidence codes were codified using Python. All code has been made freely available and is linked in the Code Availability section and all reclassified variants with evidence codes used can be found in Tables S18-19 (preprint: doi:10.1101/2024.04.11.24305690). For the MAVE data, the clinical curation and clinical strength assignment as per the ClinGen recommendations in Brnich et al. (2020) (PMID: 31892348) for or against pathogenicity or benignity of each of these MAVE datasets utilized in this study were previously published in Fayer et al. (2021) (PMID: 34793697).In brief, for BRCA1 variants, if a variant was categorized as FUNC (functional), it was assigned BS3 evidence and no PS3 evidence, whereas if it was categorized as LOF (loss of function), the variant was assigned PS3 evidence and no BS3 evidence. Variants categorized as INT (intermediate) were left unannotated. For the BRCA1 combining criteria, greater than or equal to 1 criteria of strong benign evidence was enough to reclassify the VUS as Likely Benign. This variant GRCh37:17:41197808:T>C was assigned evidence codes ['BS3', 'BP4'] and an overall classification of Likely Benign (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: SCV001237559.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
FUNCTIONAL:-0.276791005238962
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Comment:
Comment:
The p.M1827V variant (also known as c.5479A>G), located in coding exon 22 of the BRCA1 gene, results from an A to G substitution at nucleotide position 5479. The methionine at codon 1827 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
Each variant was annotated with functional scores from MAVE data which was translated into functional evidence codes. All other evidence codes and combining criteria were adhered to as closely as possible based on the ClinGen VCEP (Variant Curation Expert Panel) gene-specific recommendations. See Supplemental Figure 34 of final paper (Supp Fig. 28 in preprint: doi:10.1101/2024.04.11.24305690) for a table to see which lines of evidence we did not have data for. The ClinGen VCEPs are highly regarded as the gold-standard for gene-specific variant curation and are developed after extensive evaluation of the evidence by clinical and scientific experts for the particular gene to classify genomic variants on a spectrum from pathogenic to benign using the 2015 ACMG/AMP Variant Interpretation Guidelines as a backbone (PMID: 25741868). Reclassification of these VUS variants from gnomAD or All of Us focused only on variants originally prescribed as VUS in ClinVar. To ensure reproducibility, transparency, and increased throughput, all the procedures for annotating variants and assigning evidence codes were codified using Python. All code has been made freely available and is linked in the Code Availability section and all reclassified variants with evidence codes used can be found in Tables S18-19 (preprint: doi:10.1101/2024.04.11.24305690). For the MAVE data, the clinical curation and clinical strength assignment as per the ClinGen recommendations in Brnich et al. (2020) (PMID: 31892348) for or against pathogenicity or benignity of each of these MAVE datasets utilized in this study were previously published in Fayer et al. (2021) (PMID: 34793697).In brief, for BRCA1 variants, if a variant was categorized as FUNC (functional), it was assigned BS3 evidence and no PS3 evidence, whereas if it was categorized as LOF (loss of function), the variant was assigned PS3 evidence and no BS3 evidence. Variants categorized as INT (intermediate) were left unannotated. For the BRCA1 combining criteria, greater than or equal to 1 criteria of strong benign evidence was enough to reclassify the VUS as Likely Benign. This variant GRCh37:17:41197808:T>C was assigned evidence codes ['BS3', 'BP4'] and an overall classification of Likely Benign
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_normal
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001237559.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5479A>G, a MISSENSE variant, produced a function score of -0.28, corresponding to a functional classification of FUNCTIONAL. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5479A>G, a MISSENSE variant, produced a function score of -0.28, 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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Comment:
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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been reported not to substantially affect BRCA1 protein function (PMID: 30209399). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 844324). This variant is present in population databases (rs771606902, ExAC 0.01%). This sequence change replaces methionine with valine at codon 1827 of the BRCA1 protein (p.Met1827Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine.
Comment:
The p.M1827V variant (also known as c.5479A>G), located in coding exon 22 of the BRCA1 gene, results from an A to G substitution at nucleotide position 5479. The methionine at codon 1827 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
Each variant was annotated with functional scores from MAVE data which was translated into functional evidence codes. All other evidence codes and combining criteria were adhered to as closely as possible based on the ClinGen VCEP (Variant Curation Expert Panel) gene-specific recommendations. See Supplemental Figure 34 of final paper (Supp Fig. 28 in preprint: doi:10.1101/2024.04.11.24305690) for a table to see which lines of evidence we did not have data for. The ClinGen VCEPs are highly regarded as the gold-standard for gene-specific variant curation and are developed after extensive evaluation of the evidence by clinical and scientific experts for the particular gene to classify genomic variants on a spectrum from pathogenic to benign using the 2015 ACMG/AMP Variant Interpretation Guidelines as a backbone (PMID: 25741868). Reclassification of these VUS variants from gnomAD or All of Us focused only on variants originally prescribed as VUS in ClinVar. To ensure reproducibility, transparency, and increased throughput, all the procedures for annotating variants and assigning evidence codes were codified using Python. All code has been made freely available and is linked in the Code Availability section and all reclassified variants with evidence codes used can be found in Tables S18-19 (preprint: doi:10.1101/2024.04.11.24305690). For the MAVE data, the clinical curation and clinical strength assignment as per the ClinGen recommendations in Brnich et al. (2020) (PMID: 31892348) for or against pathogenicity or benignity of each of these MAVE datasets utilized in this study were previously published in Fayer et al. (2021) (PMID: 34793697).In brief, for BRCA1 variants, if a variant was categorized as FUNC (functional), it was assigned BS3 evidence and no PS3 evidence, whereas if it was categorized as LOF (loss of function), the variant was assigned PS3 evidence and no BS3 evidence. Variants categorized as INT (intermediate) were left unannotated. For the BRCA1 combining criteria, greater than or equal to 1 criteria of strong benign evidence was enough to reclassify the VUS as Likely Benign. This variant GRCh37:17:41197808:T>C was assigned evidence codes ['BS3', 'BP4'] and an overall classification of Likely Benign
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Evidence-based recommendations for gene-specific ACMG/AMP variant classification from the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel. | Parsons MT | American journal of human genetics | 2024 | PMID: 39142283 |
| Defining and Reducing Variant Classification Disparities. | Dawood M | medRxiv : the preprint server for health sciences | 2024 | DOI: 10.1101/2024.04.11.24305690 |
| 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 |
| Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
| https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
Text-mined citations for rs771606902 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 25, 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.