This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4352A>G (p.Glu1451Gly)
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.
(4)
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)
4
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.4352A>G (p.Glu1451Gly)
Variation ID: 480987 Accession: VCV000480987.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43082409 (GRCh38) [ NCBI UCSC ] 17: 41234426 (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 Jan 1, 2018 May 1, 2024 Nov 3, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4352A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Glu1451Gly missense NM_001407571.1:c.4139A>G NP_001394500.1:p.Glu1380Gly missense NM_001407581.1:c.4352A>G NP_001394510.1:p.Glu1451Gly missense NM_001407582.1:c.4352A>G NP_001394511.1:p.Glu1451Gly missense NM_001407583.1:c.4352A>G NP_001394512.1:p.Glu1451Gly missense NM_001407585.1:c.4352A>G NP_001394514.1:p.Glu1451Gly missense NM_001407587.1:c.4349A>G NP_001394516.1:p.Glu1450Gly missense NM_001407590.1:c.4349A>G NP_001394519.1:p.Glu1450Gly missense NM_001407591.1:c.4349A>G NP_001394520.1:p.Glu1450Gly missense NM_001407593.1:c.4352A>G NP_001394522.1:p.Glu1451Gly missense NM_001407594.1:c.4352A>G NP_001394523.1:p.Glu1451Gly missense NM_001407596.1:c.4352A>G NP_001394525.1:p.Glu1451Gly missense NM_001407597.1:c.4352A>G NP_001394526.1:p.Glu1451Gly missense NM_001407598.1:c.4352A>G NP_001394527.1:p.Glu1451Gly missense NM_001407602.1:c.4352A>G NP_001394531.1:p.Glu1451Gly missense NM_001407603.1:c.4352A>G NP_001394532.1:p.Glu1451Gly missense NM_001407605.1:c.4352A>G NP_001394534.1:p.Glu1451Gly missense NM_001407610.1:c.4349A>G NP_001394539.1:p.Glu1450Gly missense NM_001407611.1:c.4349A>G NP_001394540.1:p.Glu1450Gly missense NM_001407612.1:c.4349A>G NP_001394541.1:p.Glu1450Gly missense NM_001407613.1:c.4349A>G NP_001394542.1:p.Glu1450Gly missense NM_001407614.1:c.4349A>G NP_001394543.1:p.Glu1450Gly missense NM_001407615.1:c.4349A>G NP_001394544.1:p.Glu1450Gly missense NM_001407616.1:c.4352A>G NP_001394545.1:p.Glu1451Gly missense NM_001407617.1:c.4352A>G NP_001394546.1:p.Glu1451Gly missense NM_001407618.1:c.4352A>G NP_001394547.1:p.Glu1451Gly missense NM_001407619.1:c.4352A>G NP_001394548.1:p.Glu1451Gly missense NM_001407620.1:c.4352A>G NP_001394549.1:p.Glu1451Gly missense NM_001407621.1:c.4352A>G NP_001394550.1:p.Glu1451Gly missense NM_001407622.1:c.4352A>G NP_001394551.1:p.Glu1451Gly missense NM_001407623.1:c.4352A>G NP_001394552.1:p.Glu1451Gly missense NM_001407624.1:c.4349A>G NP_001394553.1:p.Glu1450Gly missense NM_001407625.1:c.4349A>G NP_001394554.1:p.Glu1450Gly missense NM_001407626.1:c.4349A>G NP_001394555.1:p.Glu1450Gly missense NM_001407627.1:c.4346A>G NP_001394556.1:p.Glu1449Gly missense NM_001407628.1:c.4346A>G NP_001394557.1:p.Glu1449Gly missense NM_001407629.1:c.4346A>G NP_001394558.1:p.Glu1449Gly missense NM_001407630.1:c.4346A>G NP_001394559.1:p.Glu1449Gly missense NM_001407631.1:c.4346A>G NP_001394560.1:p.Glu1449Gly missense NM_001407632.1:c.4346A>G NP_001394561.1:p.Glu1449Gly missense NM_001407633.1:c.4349A>G NP_001394562.1:p.Glu1450Gly missense NM_001407634.1:c.4349A>G NP_001394563.1:p.Glu1450Gly missense NM_001407635.1:c.4349A>G NP_001394564.1:p.Glu1450Gly missense NM_001407636.1:c.4349A>G NP_001394565.1:p.Glu1450Gly missense NM_001407637.1:c.4349A>G NP_001394566.1:p.Glu1450Gly missense NM_001407638.1:c.4349A>G NP_001394567.1:p.Glu1450Gly missense NM_001407639.1:c.4349A>G NP_001394568.1:p.Glu1450Gly missense NM_001407640.1:c.4349A>G NP_001394569.1:p.Glu1450Gly missense NM_001407641.1:c.4349A>G NP_001394570.1:p.Glu1450Gly missense NM_001407642.1:c.4349A>G NP_001394571.1:p.Glu1450Gly missense NM_001407644.1:c.4346A>G NP_001394573.1:p.Glu1449Gly missense NM_001407645.1:c.4346A>G NP_001394574.1:p.Glu1449Gly missense NM_001407646.1:c.4340A>G NP_001394575.1:p.Glu1447Gly missense NM_001407647.1:c.4340A>G NP_001394576.1:p.Glu1447Gly missense NM_001407648.1:c.4229A>G NP_001394577.1:p.Glu1410Gly missense NM_001407649.1:c.4226A>G NP_001394578.1:p.Glu1409Gly missense NM_001407652.1:c.4352A>G NP_001394581.1:p.Glu1451Gly missense NM_001407653.1:c.4274A>G NP_001394582.1:p.Glu1425Gly missense NM_001407654.1:c.4274A>G NP_001394583.1:p.Glu1425Gly missense NM_001407655.1:c.4274A>G NP_001394584.1:p.Glu1425Gly missense NM_001407656.1:c.4271A>G NP_001394585.1:p.Glu1424Gly missense NM_001407657.1:c.4274A>G NP_001394586.1:p.Glu1425Gly missense NM_001407658.1:c.4274A>G NP_001394587.1:p.Glu1425Gly missense NM_001407659.1:c.4268A>G NP_001394588.1:p.Glu1423Gly missense NM_001407660.1:c.4268A>G NP_001394589.1:p.Glu1423Gly missense NM_001407661.1:c.4271A>G NP_001394590.1:p.Glu1424Gly missense NM_001407662.1:c.4271A>G NP_001394591.1:p.Glu1424Gly missense NM_001407663.1:c.4271A>G NP_001394592.1:p.Glu1424Gly missense NM_001407664.1:c.4229A>G NP_001394593.1:p.Glu1410Gly missense NM_001407665.1:c.4229A>G NP_001394594.1:p.Glu1410Gly missense NM_001407666.1:c.4229A>G NP_001394595.1:p.Glu1410Gly missense NM_001407667.1:c.4229A>G NP_001394596.1:p.Glu1410Gly missense NM_001407668.1:c.4229A>G NP_001394597.1:p.Glu1410Gly missense NM_001407669.1:c.4229A>G NP_001394598.1:p.Glu1410Gly missense NM_001407670.1:c.4226A>G NP_001394599.1:p.Glu1409Gly missense NM_001407671.1:c.4226A>G NP_001394600.1:p.Glu1409Gly missense NM_001407672.1:c.4226A>G NP_001394601.1:p.Glu1409Gly missense NM_001407673.1:c.4226A>G NP_001394602.1:p.Glu1409Gly missense NM_001407674.1:c.4226A>G NP_001394603.1:p.Glu1409Gly missense NM_001407675.1:c.4226A>G NP_001394604.1:p.Glu1409Gly missense NM_001407676.1:c.4226A>G NP_001394605.1:p.Glu1409Gly missense NM_001407677.1:c.4229A>G NP_001394606.1:p.Glu1410Gly missense NM_001407678.1:c.4229A>G NP_001394607.1:p.Glu1410Gly missense NM_001407679.1:c.4229A>G NP_001394608.1:p.Glu1410Gly missense NM_001407680.1:c.4229A>G NP_001394609.1:p.Glu1410Gly missense NM_001407681.1:c.4226A>G NP_001394610.1:p.Glu1409Gly missense NM_001407682.1:c.4226A>G NP_001394611.1:p.Glu1409Gly missense NM_001407683.1:c.4226A>G NP_001394612.1:p.Glu1409Gly missense NM_001407684.1:c.4352A>G NP_001394613.1:p.Glu1451Gly missense NM_001407685.1:c.4223A>G NP_001394614.1:p.Glu1408Gly missense NM_001407686.1:c.4223A>G NP_001394615.1:p.Glu1408Gly missense NM_001407687.1:c.4223A>G NP_001394616.1:p.Glu1408Gly missense NM_001407688.1:c.4226A>G NP_001394617.1:p.Glu1409Gly missense NM_001407689.1:c.4226A>G NP_001394618.1:p.Glu1409Gly missense NM_001407690.1:c.4223A>G NP_001394619.1:p.Glu1408Gly missense NM_001407691.1:c.4223A>G NP_001394620.1:p.Glu1408Gly missense NM_001407692.1:c.4211A>G NP_001394621.1:p.Glu1404Gly missense NM_001407694.1:c.4211A>G NP_001394623.1:p.Glu1404Gly missense NM_001407695.1:c.4211A>G NP_001394624.1:p.Glu1404Gly missense NM_001407696.1:c.4211A>G NP_001394625.1:p.Glu1404Gly missense NM_001407697.1:c.4211A>G NP_001394626.1:p.Glu1404Gly missense NM_001407698.1:c.4211A>G NP_001394627.1:p.Glu1404Gly missense NM_001407724.1:c.4211A>G NP_001394653.1:p.Glu1404Gly missense NM_001407725.1:c.4211A>G NP_001394654.1:p.Glu1404Gly missense NM_001407726.1:c.4211A>G NP_001394655.1:p.Glu1404Gly missense NM_001407727.1:c.4211A>G NP_001394656.1:p.Glu1404Gly missense NM_001407728.1:c.4211A>G NP_001394657.1:p.Glu1404Gly missense NM_001407729.1:c.4211A>G NP_001394658.1:p.Glu1404Gly missense NM_001407730.1:c.4211A>G NP_001394659.1:p.Glu1404Gly missense NM_001407731.1:c.4211A>G NP_001394660.1:p.Glu1404Gly missense NM_001407732.1:c.4211A>G NP_001394661.1:p.Glu1404Gly missense NM_001407733.1:c.4211A>G NP_001394662.1:p.Glu1404Gly missense NM_001407734.1:c.4211A>G NP_001394663.1:p.Glu1404Gly missense NM_001407735.1:c.4211A>G NP_001394664.1:p.Glu1404Gly missense NM_001407736.1:c.4211A>G NP_001394665.1:p.Glu1404Gly missense NM_001407737.1:c.4211A>G NP_001394666.1:p.Glu1404Gly missense NM_001407738.1:c.4211A>G NP_001394667.1:p.Glu1404Gly missense NM_001407739.1:c.4211A>G NP_001394668.1:p.Glu1404Gly missense NM_001407740.1:c.4208A>G NP_001394669.1:p.Glu1403Gly missense NM_001407741.1:c.4208A>G NP_001394670.1:p.Glu1403Gly missense NM_001407742.1:c.4208A>G NP_001394671.1:p.Glu1403Gly missense NM_001407743.1:c.4208A>G NP_001394672.1:p.Glu1403Gly missense NM_001407744.1:c.4208A>G NP_001394673.1:p.Glu1403Gly missense NM_001407745.1:c.4208A>G NP_001394674.1:p.Glu1403Gly missense NM_001407746.1:c.4208A>G NP_001394675.1:p.Glu1403Gly missense NM_001407747.1:c.4208A>G NP_001394676.1:p.Glu1403Gly missense NM_001407748.1:c.4208A>G NP_001394677.1:p.Glu1403Gly missense NM_001407749.1:c.4208A>G NP_001394678.1:p.Glu1403Gly missense NM_001407750.1:c.4208A>G NP_001394679.1:p.Glu1403Gly missense NM_001407751.1:c.4208A>G NP_001394680.1:p.Glu1403Gly missense NM_001407752.1:c.4208A>G NP_001394681.1:p.Glu1403Gly missense NM_001407838.1:c.4208A>G NP_001394767.1:p.Glu1403Gly missense NM_001407839.1:c.4208A>G NP_001394768.1:p.Glu1403Gly missense NM_001407841.1:c.4208A>G NP_001394770.1:p.Glu1403Gly missense NM_001407842.1:c.4208A>G NP_001394771.1:p.Glu1403Gly missense NM_001407843.1:c.4208A>G NP_001394772.1:p.Glu1403Gly missense NM_001407844.1:c.4208A>G NP_001394773.1:p.Glu1403Gly missense NM_001407845.1:c.4208A>G NP_001394774.1:p.Glu1403Gly missense NM_001407846.1:c.4208A>G NP_001394775.1:p.Glu1403Gly missense NM_001407847.1:c.4205A>G NP_001394776.1:p.Glu1402Gly missense NM_001407848.1:c.4205A>G NP_001394777.1:p.Glu1402Gly missense NM_001407849.1:c.4205A>G NP_001394778.1:p.Glu1402Gly missense NM_001407850.1:c.4208A>G NP_001394779.1:p.Glu1403Gly missense NM_001407851.1:c.4208A>G NP_001394780.1:p.Glu1403Gly missense NM_001407852.1:c.4208A>G NP_001394781.1:p.Glu1403Gly missense NM_001407853.1:c.4139A>G NP_001394782.1:p.Glu1380Gly missense NM_001407854.1:c.4352A>G NP_001394783.1:p.Glu1451Gly missense NM_001407858.1:c.4352A>G NP_001394787.1:p.Glu1451Gly missense NM_001407859.1:c.4352A>G NP_001394788.1:p.Glu1451Gly missense NM_001407860.1:c.4349A>G NP_001394789.1:p.Glu1450Gly missense NM_001407861.1:c.4349A>G NP_001394790.1:p.Glu1450Gly missense NM_001407862.1:c.4151A>G NP_001394791.1:p.Glu1384Gly missense NM_001407863.1:c.4229A>G NP_001394792.1:p.Glu1410Gly missense NM_001407874.1:c.4148A>G NP_001394803.1:p.Glu1383Gly missense NM_001407875.1:c.4148A>G NP_001394804.1:p.Glu1383Gly missense NM_001407879.1:c.4142A>G NP_001394808.1:p.Glu1381Gly missense NM_001407881.1:c.4142A>G NP_001394810.1:p.Glu1381Gly missense NM_001407882.1:c.4142A>G NP_001394811.1:p.Glu1381Gly missense NM_001407884.1:c.4142A>G NP_001394813.1:p.Glu1381Gly missense NM_001407885.1:c.4142A>G NP_001394814.1:p.Glu1381Gly missense NM_001407886.1:c.4142A>G NP_001394815.1:p.Glu1381Gly missense NM_001407887.1:c.4142A>G NP_001394816.1:p.Glu1381Gly missense NM_001407889.1:c.4142A>G NP_001394818.1:p.Glu1381Gly missense NM_001407894.1:c.4139A>G NP_001394823.1:p.Glu1380Gly missense NM_001407895.1:c.4139A>G NP_001394824.1:p.Glu1380Gly missense NM_001407896.1:c.4139A>G NP_001394825.1:p.Glu1380Gly missense NM_001407897.1:c.4139A>G NP_001394826.1:p.Glu1380Gly missense NM_001407898.1:c.4139A>G NP_001394827.1:p.Glu1380Gly missense NM_001407899.1:c.4139A>G NP_001394828.1:p.Glu1380Gly missense NM_001407900.1:c.4142A>G NP_001394829.1:p.Glu1381Gly missense NM_001407902.1:c.4142A>G NP_001394831.1:p.Glu1381Gly missense NM_001407904.1:c.4142A>G NP_001394833.1:p.Glu1381Gly missense NM_001407906.1:c.4142A>G NP_001394835.1:p.Glu1381Gly missense NM_001407907.1:c.4139A>G NP_001394836.1:p.Glu1380Gly missense NM_001407908.1:c.4139A>G NP_001394837.1:p.Glu1380Gly missense NM_001407909.1:c.4139A>G NP_001394838.1:p.Glu1380Gly missense NM_001407910.1:c.4139A>G NP_001394839.1:p.Glu1380Gly missense NM_001407915.1:c.4136A>G NP_001394844.1:p.Glu1379Gly missense NM_001407916.1:c.4139A>G NP_001394845.1:p.Glu1380Gly missense NM_001407917.1:c.4139A>G NP_001394846.1:p.Glu1380Gly missense NM_001407918.1:c.4139A>G NP_001394847.1:p.Glu1380Gly missense NM_001407919.1:c.4229A>G NP_001394848.1:p.Glu1410Gly missense NM_001407920.1:c.4088A>G NP_001394849.1:p.Glu1363Gly missense NM_001407921.1:c.4088A>G NP_001394850.1:p.Glu1363Gly missense NM_001407922.1:c.4088A>G NP_001394851.1:p.Glu1363Gly missense NM_001407923.1:c.4088A>G NP_001394852.1:p.Glu1363Gly missense NM_001407924.1:c.4088A>G NP_001394853.1:p.Glu1363Gly missense NM_001407925.1:c.4088A>G NP_001394854.1:p.Glu1363Gly missense NM_001407926.1:c.4088A>G NP_001394855.1:p.Glu1363Gly missense NM_001407927.1:c.4088A>G NP_001394856.1:p.Glu1363Gly missense NM_001407928.1:c.4088A>G NP_001394857.1:p.Glu1363Gly missense NM_001407929.1:c.4088A>G NP_001394858.1:p.Glu1363Gly missense NM_001407930.1:c.4085A>G NP_001394859.1:p.Glu1362Gly missense NM_001407931.1:c.4085A>G NP_001394860.1:p.Glu1362Gly missense NM_001407932.1:c.4085A>G NP_001394861.1:p.Glu1362Gly missense NM_001407933.1:c.4085A>G NP_001394862.1:p.Glu1362Gly missense NM_001407934.1:c.4082A>G NP_001394863.1:p.Glu1361Gly missense NM_001407935.1:c.4085A>G NP_001394864.1:p.Glu1362Gly missense NM_001407936.1:c.4085A>G NP_001394865.1:p.Glu1362Gly missense NM_001407937.1:c.4229A>G NP_001394866.1:p.Glu1410Gly missense NM_001407938.1:c.4229A>G NP_001394867.1:p.Glu1410Gly missense NM_001407939.1:c.4229A>G NP_001394868.1:p.Glu1410Gly missense NM_001407940.1:c.4226A>G NP_001394869.1:p.Glu1409Gly missense NM_001407941.1:c.4226A>G NP_001394870.1:p.Glu1409Gly missense NM_001407942.1:c.4211A>G NP_001394871.1:p.Glu1404Gly missense NM_001407943.1:c.4208A>G NP_001394872.1:p.Glu1403Gly missense NM_001407944.1:c.4211A>G NP_001394873.1:p.Glu1404Gly missense NM_001407945.1:c.4211A>G NP_001394874.1:p.Glu1404Gly missense NM_001407946.1:c.4019A>G NP_001394875.1:p.Glu1340Gly missense NM_001407947.1:c.4019A>G NP_001394876.1:p.Glu1340Gly missense NM_001407948.1:c.4019A>G NP_001394877.1:p.Glu1340Gly missense NM_001407949.1:c.4019A>G NP_001394878.1:p.Glu1340Gly missense NM_001407950.1:c.4019A>G NP_001394879.1:p.Glu1340Gly missense NM_001407951.1:c.4019A>G NP_001394880.1:p.Glu1340Gly missense NM_001407952.1:c.4016A>G NP_001394881.1:p.Glu1339Gly missense NM_001407953.1:c.4016A>G NP_001394882.1:p.Glu1339Gly missense NM_001407954.1:c.4016A>G NP_001394883.1:p.Glu1339Gly missense NM_001407955.1:c.4016A>G NP_001394884.1:p.Glu1339Gly missense NM_001407956.1:c.4013A>G NP_001394885.1:p.Glu1338Gly missense NM_001407957.1:c.4016A>G NP_001394886.1:p.Glu1339Gly missense NM_001407958.1:c.4016A>G NP_001394887.1:p.Glu1339Gly missense NM_001407959.1:c.3971A>G NP_001394888.1:p.Glu1324Gly missense NM_001407960.1:c.3971A>G NP_001394889.1:p.Glu1324Gly missense NM_001407962.1:c.3968A>G NP_001394891.1:p.Glu1323Gly missense NM_001407963.1:c.3968A>G NP_001394892.1:p.Glu1323Gly missense NM_001407964.1:c.4208A>G NP_001394893.1:p.Glu1403Gly missense NM_001407965.1:c.3845A>G NP_001394894.1:p.Glu1282Gly missense NM_001407966.1:c.3464A>G NP_001394895.1:p.Glu1155Gly missense NM_001407967.1:c.3464A>G NP_001394896.1:p.Glu1155Gly missense NM_001407968.1:c.1748A>G NP_001394897.1:p.Glu583Gly missense NM_001407969.1:c.1745A>G NP_001394898.1:p.Glu582Gly missense NM_001407970.1:c.1043A>G NP_001394899.1:p.Glu348Gly missense NM_001407971.1:c.1043A>G NP_001394900.1:p.Glu348Gly missense NM_001407972.1:c.1040A>G NP_001394901.1:p.Glu347Gly missense NM_001407973.1:c.1043A>G NP_001394902.1:p.Glu348Gly missense NM_001407974.1:c.1043A>G NP_001394903.1:p.Glu348Gly missense NM_001407975.1:c.1043A>G NP_001394904.1:p.Glu348Gly missense NM_001407976.1:c.1043A>G NP_001394905.1:p.Glu348Gly missense NM_001407977.1:c.1043A>G NP_001394906.1:p.Glu348Gly missense NM_001407978.1:c.1043A>G NP_001394907.1:p.Glu348Gly missense NM_001407979.1:c.1040A>G NP_001394908.1:p.Glu347Gly missense NM_001407980.1:c.1040A>G NP_001394909.1:p.Glu347Gly missense NM_001407981.1:c.1040A>G NP_001394910.1:p.Glu347Gly missense NM_001407982.1:c.1040A>G NP_001394911.1:p.Glu347Gly missense NM_001407983.1:c.1040A>G NP_001394912.1:p.Glu347Gly missense NM_001407984.1:c.1040A>G NP_001394913.1:p.Glu347Gly missense NM_001407985.1:c.1040A>G NP_001394914.1:p.Glu347Gly missense NM_001407986.1:c.1040A>G NP_001394915.1:p.Glu347Gly missense NM_001407990.1:c.1040A>G NP_001394919.1:p.Glu347Gly missense NM_001407991.1:c.1040A>G NP_001394920.1:p.Glu347Gly missense NM_001407992.1:c.1040A>G NP_001394921.1:p.Glu347Gly missense NM_001407993.1:c.1043A>G NP_001394922.1:p.Glu348Gly missense NM_001408392.1:c.1040A>G NP_001395321.1:p.Glu347Gly missense NM_001408396.1:c.1040A>G NP_001395325.1:p.Glu347Gly missense NM_001408397.1:c.1040A>G NP_001395326.1:p.Glu347Gly missense NM_001408398.1:c.1040A>G NP_001395327.1:p.Glu347Gly missense NM_001408399.1:c.1040A>G NP_001395328.1:p.Glu347Gly missense NM_001408400.1:c.1037A>G NP_001395329.1:p.Glu346Gly missense NM_001408401.1:c.1037A>G NP_001395330.1:p.Glu346Gly missense NM_001408402.1:c.1037A>G NP_001395331.1:p.Glu346Gly missense NM_001408403.1:c.1040A>G NP_001395332.1:p.Glu347Gly missense NM_001408404.1:c.1040A>G NP_001395333.1:p.Glu347Gly missense NM_001408406.1:c.1034A>G NP_001395335.1:p.Glu345Gly missense NM_001408407.1:c.1037A>G NP_001395336.1:p.Glu346Gly missense NM_001408408.1:c.1034A>G NP_001395337.1:p.Glu345Gly missense NM_001408409.1:c.965A>G NP_001395338.1:p.Glu322Gly missense NM_001408410.1:c.902A>G NP_001395339.1:p.Glu301Gly missense NM_001408411.1:c.965A>G NP_001395340.1:p.Glu322Gly missense NM_001408412.1:c.965A>G NP_001395341.1:p.Glu322Gly missense NM_001408413.1:c.962A>G NP_001395342.1:p.Glu321Gly missense NM_001408414.1:c.965A>G NP_001395343.1:p.Glu322Gly missense NM_001408415.1:c.965A>G NP_001395344.1:p.Glu322Gly missense NM_001408416.1:c.962A>G NP_001395345.1:p.Glu321Gly missense NM_001408418.1:c.926A>G NP_001395347.1:p.Glu309Gly missense NM_001408419.1:c.926A>G NP_001395348.1:p.Glu309Gly missense NM_001408420.1:c.926A>G NP_001395349.1:p.Glu309Gly missense NM_001408421.1:c.923A>G NP_001395350.1:p.Glu308Gly missense NM_001408422.1:c.926A>G NP_001395351.1:p.Glu309Gly missense NM_001408423.1:c.926A>G NP_001395352.1:p.Glu309Gly missense NM_001408424.1:c.923A>G NP_001395353.1:p.Glu308Gly missense NM_001408425.1:c.920A>G NP_001395354.1:p.Glu307Gly missense NM_001408426.1:c.920A>G NP_001395355.1:p.Glu307Gly missense NM_001408427.1:c.920A>G NP_001395356.1:p.Glu307Gly missense NM_001408428.1:c.920A>G NP_001395357.1:p.Glu307Gly missense NM_001408429.1:c.920A>G NP_001395358.1:p.Glu307Gly missense NM_001408430.1:c.920A>G NP_001395359.1:p.Glu307Gly missense NM_001408431.1:c.923A>G NP_001395360.1:p.Glu308Gly missense NM_001408432.1:c.917A>G NP_001395361.1:p.Glu306Gly missense NM_001408433.1:c.917A>G NP_001395362.1:p.Glu306Gly missense NM_001408434.1:c.917A>G NP_001395363.1:p.Glu306Gly missense NM_001408435.1:c.917A>G NP_001395364.1:p.Glu306Gly missense NM_001408436.1:c.920A>G NP_001395365.1:p.Glu307Gly missense NM_001408437.1:c.920A>G NP_001395366.1:p.Glu307Gly missense NM_001408438.1:c.920A>G NP_001395367.1:p.Glu307Gly missense NM_001408439.1:c.920A>G NP_001395368.1:p.Glu307Gly missense NM_001408440.1:c.920A>G NP_001395369.1:p.Glu307Gly missense NM_001408441.1:c.917A>G NP_001395370.1:p.Glu306Gly missense NM_001408442.1:c.917A>G NP_001395371.1:p.Glu306Gly missense NM_001408443.1:c.917A>G NP_001395372.1:p.Glu306Gly missense NM_001408444.1:c.917A>G NP_001395373.1:p.Glu306Gly missense NM_001408445.1:c.917A>G NP_001395374.1:p.Glu306Gly missense NM_001408446.1:c.917A>G NP_001395375.1:p.Glu306Gly missense NM_001408447.1:c.917A>G NP_001395376.1:p.Glu306Gly missense NM_001408448.1:c.917A>G NP_001395377.1:p.Glu306Gly missense NM_001408450.1:c.917A>G NP_001395379.1:p.Glu306Gly missense NM_001408451.1:c.908A>G NP_001395380.1:p.Glu303Gly missense NM_001408452.1:c.902A>G NP_001395381.1:p.Glu301Gly missense NM_001408453.1:c.902A>G NP_001395382.1:p.Glu301Gly missense NM_001408454.1:c.902A>G NP_001395383.1:p.Glu301Gly missense NM_001408455.1:c.902A>G NP_001395384.1:p.Glu301Gly missense NM_001408456.1:c.902A>G NP_001395385.1:p.Glu301Gly missense NM_001408457.1:c.902A>G NP_001395386.1:p.Glu301Gly missense NM_001408458.1:c.902A>G NP_001395387.1:p.Glu301Gly missense NM_001408459.1:c.902A>G NP_001395388.1:p.Glu301Gly missense NM_001408460.1:c.902A>G NP_001395389.1:p.Glu301Gly missense NM_001408461.1:c.902A>G NP_001395390.1:p.Glu301Gly missense NM_001408462.1:c.899A>G NP_001395391.1:p.Glu300Gly missense NM_001408463.1:c.899A>G NP_001395392.1:p.Glu300Gly missense NM_001408464.1:c.899A>G NP_001395393.1:p.Glu300Gly missense NM_001408465.1:c.899A>G NP_001395394.1:p.Glu300Gly missense NM_001408466.1:c.899A>G NP_001395395.1:p.Glu300Gly missense NM_001408467.1:c.899A>G NP_001395396.1:p.Glu300Gly missense NM_001408468.1:c.899A>G NP_001395397.1:p.Glu300Gly missense NM_001408469.1:c.899A>G NP_001395398.1:p.Glu300Gly missense NM_001408470.1:c.896A>G NP_001395399.1:p.Glu299Gly missense NM_001408472.1:c.1040A>G NP_001395401.1:p.Glu347Gly missense NM_001408473.1:c.1040A>G NP_001395402.1:p.Glu347Gly missense NM_001408474.1:c.842A>G NP_001395403.1:p.Glu281Gly missense NM_001408475.1:c.839A>G NP_001395404.1:p.Glu280Gly missense NM_001408476.1:c.842A>G NP_001395405.1:p.Glu281Gly missense NM_001408478.1:c.833A>G NP_001395407.1:p.Glu278Gly missense NM_001408479.1:c.833A>G NP_001395408.1:p.Glu278Gly missense NM_001408480.1:c.833A>G NP_001395409.1:p.Glu278Gly missense NM_001408481.1:c.833A>G NP_001395410.1:p.Glu278Gly missense NM_001408482.1:c.833A>G NP_001395411.1:p.Glu278Gly missense NM_001408483.1:c.833A>G NP_001395412.1:p.Glu278Gly missense NM_001408484.1:c.833A>G NP_001395413.1:p.Glu278Gly missense NM_001408485.1:c.833A>G NP_001395414.1:p.Glu278Gly missense NM_001408489.1:c.830A>G NP_001395418.1:p.Glu277Gly missense NM_001408490.1:c.830A>G NP_001395419.1:p.Glu277Gly missense NM_001408491.1:c.830A>G NP_001395420.1:p.Glu277Gly missense NM_001408492.1:c.830A>G NP_001395421.1:p.Glu277Gly missense NM_001408493.1:c.830A>G NP_001395422.1:p.Glu277Gly missense NM_001408494.1:c.803A>G NP_001395423.1:p.Glu268Gly missense NM_001408495.1:c.800A>G NP_001395424.1:p.Glu267Gly missense NM_001408496.1:c.779A>G NP_001395425.1:p.Glu260Gly missense NM_001408497.1:c.779A>G NP_001395426.1:p.Glu260Gly missense NM_001408498.1:c.779A>G NP_001395427.1:p.Glu260Gly missense NM_001408499.1:c.779A>G NP_001395428.1:p.Glu260Gly missense NM_001408500.1:c.779A>G NP_001395429.1:p.Glu260Gly missense NM_001408501.1:c.779A>G NP_001395430.1:p.Glu260Gly missense NM_001408502.1:c.710A>G NP_001395431.1:p.Glu237Gly missense NM_001408503.1:c.776A>G NP_001395432.1:p.Glu259Gly missense NM_001408504.1:c.776A>G NP_001395433.1:p.Glu259Gly missense NM_001408505.1:c.776A>G NP_001395434.1:p.Glu259Gly missense NM_001408506.1:c.716A>G NP_001395435.1:p.Glu239Gly missense NM_001408507.1:c.713A>G NP_001395436.1:p.Glu238Gly missense NM_001408508.1:c.704A>G NP_001395437.1:p.Glu235Gly missense NM_001408509.1:c.704A>G NP_001395438.1:p.Glu235Gly missense NM_001408510.1:c.662A>G NP_001395439.1:p.Glu221Gly missense NM_001408511.1:c.659A>G NP_001395440.1:p.Glu220Gly missense NM_001408512.1:c.539A>G NP_001395441.1:p.Glu180Gly missense NM_001408513.1:c.830A>G NP_001395442.1:p.Glu277Gly missense NM_001408514.1:c.833A>G NP_001395443.1:p.Glu278Gly missense NM_007297.4:c.4211A>G NP_009228.2:p.Glu1404Gly missense NM_007298.4:c.1043A>G NP_009229.2:p.Glu348Gly missense NM_007299.4:c.1043A>G NP_009230.2:p.Glu348Gly missense NM_007300.4:c.4352A>G NP_009231.2:p.Glu1451Gly missense NM_007304.2:c.1043A>G NP_009235.2:p.Glu348Gly missense NR_027676.2:n.4529A>G non-coding transcript variant NC_000017.11:g.43082409T>C NC_000017.10:g.41234426T>C NG_005905.2:g.135575A>G LRG_292:g.135575A>G LRG_292t1:c.4352A>G LRG_292p1:p.Glu1451Gly - Protein change
- E1451G, E1404G, E348G, E1339G, E1402G, E1450G, E180G, E238G, E268G, E300G, E306G, E307G, E309G, E345G, E583G, E1323G, E1324G, E1362G, E1381G, E1384G, E1408G, E1423G, E220G, E235G, E277G, E299G, E301G, E321G, E322G, E1155G, E1282G, E1338G, E1361G, E1379G, E1380G, E1383G, E1403G, E1410G, E1424G, E1425G, E1447G, E237G, E239G, E259G, E260G, E267G, E281G, E308G, E346G, E582G, E1340G, E1363G, E1409G, E1449G, E221G, E278G, E280G, E303G, E347G
- Other names
- -
- Canonical SPDI
- NC_000017.11:43082408:T:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13044 | 14850 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Sep 8, 2020 | RCV000563313.9 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Nov 3, 2022 | RCV000637803.7 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 13, 2018 | RCV001124850.5 |
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
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001283847.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
|
|
|
Uncertain significance
(Sep 08, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV001358178.2
First in ClinVar: Jun 22, 2020 Last updated: Jun 19, 2021 |
Comment:
This missense variant replaces glutamic acid with glycine at codon 1451 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein … (more)
This missense variant replaces glutamic acid with glycine at codon 1451 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The 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)
|
|
|
Uncertain significance
(Nov 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000759282.5
First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1451 of the BRCA1 protein … (more)
This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1451 of the BRCA1 protein (p.Glu1451Gly). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 480987). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). (less)
|
|
|
Likely benign
(Jan 13, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000665026.5
First in ClinVar: Jan 01, 2018 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)
|
Comment:
Comment:
This missense variant replaces glutamic acid with glycine at codon 1451 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The 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.
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1451 of the BRCA1 protein (p.Glu1451Gly). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 480987). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency).
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 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.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Comment:
This missense variant replaces glutamic acid with glycine at codon 1451 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The 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.
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1451 of the BRCA1 protein (p.Glu1451Gly). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 480987). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency).
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 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.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs949793708 ...
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 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.