IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000152
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4255G>C (p.Glu1419Gln)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Benign
Aug 2015 by
Evidence-based…
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.4255G>C (p.Glu1419Gln)
Variation ID: 55154 Accession: VCV000055154.23
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43082506 (GRCh38) [ NCBI UCSC ] 17: 41234523 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 May 1, 2024 Aug 10, 2015 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4255G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Glu1419Gln missense NM_001407571.1:c.4042G>C NP_001394500.1:p.Glu1348Gln missense NM_001407581.1:c.4255G>C NP_001394510.1:p.Glu1419Gln missense NM_001407582.1:c.4255G>C NP_001394511.1:p.Glu1419Gln missense NM_001407583.1:c.4255G>C NP_001394512.1:p.Glu1419Gln missense NM_001407585.1:c.4255G>C NP_001394514.1:p.Glu1419Gln missense NM_001407587.1:c.4252G>C NP_001394516.1:p.Glu1418Gln missense NM_001407590.1:c.4252G>C NP_001394519.1:p.Glu1418Gln missense NM_001407591.1:c.4252G>C NP_001394520.1:p.Glu1418Gln missense NM_001407593.1:c.4255G>C NP_001394522.1:p.Glu1419Gln missense NM_001407594.1:c.4255G>C NP_001394523.1:p.Glu1419Gln missense NM_001407596.1:c.4255G>C NP_001394525.1:p.Glu1419Gln missense NM_001407597.1:c.4255G>C NP_001394526.1:p.Glu1419Gln missense NM_001407598.1:c.4255G>C NP_001394527.1:p.Glu1419Gln missense NM_001407602.1:c.4255G>C NP_001394531.1:p.Glu1419Gln missense NM_001407603.1:c.4255G>C NP_001394532.1:p.Glu1419Gln missense NM_001407605.1:c.4255G>C NP_001394534.1:p.Glu1419Gln missense NM_001407610.1:c.4252G>C NP_001394539.1:p.Glu1418Gln missense NM_001407611.1:c.4252G>C NP_001394540.1:p.Glu1418Gln missense NM_001407612.1:c.4252G>C NP_001394541.1:p.Glu1418Gln missense NM_001407613.1:c.4252G>C NP_001394542.1:p.Glu1418Gln missense NM_001407614.1:c.4252G>C NP_001394543.1:p.Glu1418Gln missense NM_001407615.1:c.4252G>C NP_001394544.1:p.Glu1418Gln missense NM_001407616.1:c.4255G>C NP_001394545.1:p.Glu1419Gln missense NM_001407617.1:c.4255G>C NP_001394546.1:p.Glu1419Gln missense NM_001407618.1:c.4255G>C NP_001394547.1:p.Glu1419Gln missense NM_001407619.1:c.4255G>C NP_001394548.1:p.Glu1419Gln missense NM_001407620.1:c.4255G>C NP_001394549.1:p.Glu1419Gln missense NM_001407621.1:c.4255G>C NP_001394550.1:p.Glu1419Gln missense NM_001407622.1:c.4255G>C NP_001394551.1:p.Glu1419Gln missense NM_001407623.1:c.4255G>C NP_001394552.1:p.Glu1419Gln missense NM_001407624.1:c.4252G>C NP_001394553.1:p.Glu1418Gln missense NM_001407625.1:c.4252G>C NP_001394554.1:p.Glu1418Gln missense NM_001407626.1:c.4252G>C NP_001394555.1:p.Glu1418Gln missense NM_001407627.1:c.4249G>C NP_001394556.1:p.Glu1417Gln missense NM_001407628.1:c.4249G>C NP_001394557.1:p.Glu1417Gln missense NM_001407629.1:c.4249G>C NP_001394558.1:p.Glu1417Gln missense NM_001407630.1:c.4249G>C NP_001394559.1:p.Glu1417Gln missense NM_001407631.1:c.4249G>C NP_001394560.1:p.Glu1417Gln missense NM_001407632.1:c.4249G>C NP_001394561.1:p.Glu1417Gln missense NM_001407633.1:c.4252G>C NP_001394562.1:p.Glu1418Gln missense NM_001407634.1:c.4252G>C NP_001394563.1:p.Glu1418Gln missense NM_001407635.1:c.4252G>C NP_001394564.1:p.Glu1418Gln missense NM_001407636.1:c.4252G>C NP_001394565.1:p.Glu1418Gln missense NM_001407637.1:c.4252G>C NP_001394566.1:p.Glu1418Gln missense NM_001407638.1:c.4252G>C NP_001394567.1:p.Glu1418Gln missense NM_001407639.1:c.4252G>C NP_001394568.1:p.Glu1418Gln missense NM_001407640.1:c.4252G>C NP_001394569.1:p.Glu1418Gln missense NM_001407641.1:c.4252G>C NP_001394570.1:p.Glu1418Gln missense NM_001407642.1:c.4252G>C NP_001394571.1:p.Glu1418Gln missense NM_001407644.1:c.4249G>C NP_001394573.1:p.Glu1417Gln missense NM_001407645.1:c.4249G>C NP_001394574.1:p.Glu1417Gln missense NM_001407646.1:c.4243G>C NP_001394575.1:p.Glu1415Gln missense NM_001407647.1:c.4243G>C NP_001394576.1:p.Glu1415Gln missense NM_001407648.1:c.4132G>C NP_001394577.1:p.Glu1378Gln missense NM_001407649.1:c.4129G>C NP_001394578.1:p.Glu1377Gln missense NM_001407652.1:c.4255G>C NP_001394581.1:p.Glu1419Gln missense NM_001407653.1:c.4177G>C NP_001394582.1:p.Glu1393Gln missense NM_001407654.1:c.4177G>C NP_001394583.1:p.Glu1393Gln missense NM_001407655.1:c.4177G>C NP_001394584.1:p.Glu1393Gln missense NM_001407656.1:c.4174G>C NP_001394585.1:p.Glu1392Gln missense NM_001407657.1:c.4177G>C NP_001394586.1:p.Glu1393Gln missense NM_001407658.1:c.4177G>C NP_001394587.1:p.Glu1393Gln missense NM_001407659.1:c.4171G>C NP_001394588.1:p.Glu1391Gln missense NM_001407660.1:c.4171G>C NP_001394589.1:p.Glu1391Gln missense NM_001407661.1:c.4174G>C NP_001394590.1:p.Glu1392Gln missense NM_001407662.1:c.4174G>C NP_001394591.1:p.Glu1392Gln missense NM_001407663.1:c.4174G>C NP_001394592.1:p.Glu1392Gln missense NM_001407664.1:c.4132G>C NP_001394593.1:p.Glu1378Gln missense NM_001407665.1:c.4132G>C NP_001394594.1:p.Glu1378Gln missense NM_001407666.1:c.4132G>C NP_001394595.1:p.Glu1378Gln missense NM_001407667.1:c.4132G>C NP_001394596.1:p.Glu1378Gln missense NM_001407668.1:c.4132G>C NP_001394597.1:p.Glu1378Gln missense NM_001407669.1:c.4132G>C NP_001394598.1:p.Glu1378Gln missense NM_001407670.1:c.4129G>C NP_001394599.1:p.Glu1377Gln missense NM_001407671.1:c.4129G>C NP_001394600.1:p.Glu1377Gln missense NM_001407672.1:c.4129G>C NP_001394601.1:p.Glu1377Gln missense NM_001407673.1:c.4129G>C NP_001394602.1:p.Glu1377Gln missense NM_001407674.1:c.4129G>C NP_001394603.1:p.Glu1377Gln missense NM_001407675.1:c.4129G>C NP_001394604.1:p.Glu1377Gln missense NM_001407676.1:c.4129G>C NP_001394605.1:p.Glu1377Gln missense NM_001407677.1:c.4132G>C NP_001394606.1:p.Glu1378Gln missense NM_001407678.1:c.4132G>C NP_001394607.1:p.Glu1378Gln missense NM_001407679.1:c.4132G>C NP_001394608.1:p.Glu1378Gln missense NM_001407680.1:c.4132G>C NP_001394609.1:p.Glu1378Gln missense NM_001407681.1:c.4129G>C NP_001394610.1:p.Glu1377Gln missense NM_001407682.1:c.4129G>C NP_001394611.1:p.Glu1377Gln missense NM_001407683.1:c.4129G>C NP_001394612.1:p.Glu1377Gln missense NM_001407684.1:c.4255G>C NP_001394613.1:p.Glu1419Gln missense NM_001407685.1:c.4126G>C NP_001394614.1:p.Glu1376Gln missense NM_001407686.1:c.4126G>C NP_001394615.1:p.Glu1376Gln missense NM_001407687.1:c.4126G>C NP_001394616.1:p.Glu1376Gln missense NM_001407688.1:c.4129G>C NP_001394617.1:p.Glu1377Gln missense NM_001407689.1:c.4129G>C NP_001394618.1:p.Glu1377Gln missense NM_001407690.1:c.4126G>C NP_001394619.1:p.Glu1376Gln missense NM_001407691.1:c.4126G>C NP_001394620.1:p.Glu1376Gln missense NM_001407692.1:c.4114G>C NP_001394621.1:p.Glu1372Gln missense NM_001407694.1:c.4114G>C NP_001394623.1:p.Glu1372Gln missense NM_001407695.1:c.4114G>C NP_001394624.1:p.Glu1372Gln missense NM_001407696.1:c.4114G>C NP_001394625.1:p.Glu1372Gln missense NM_001407697.1:c.4114G>C NP_001394626.1:p.Glu1372Gln missense NM_001407698.1:c.4114G>C NP_001394627.1:p.Glu1372Gln missense NM_001407724.1:c.4114G>C NP_001394653.1:p.Glu1372Gln missense NM_001407725.1:c.4114G>C NP_001394654.1:p.Glu1372Gln missense NM_001407726.1:c.4114G>C NP_001394655.1:p.Glu1372Gln missense NM_001407727.1:c.4114G>C NP_001394656.1:p.Glu1372Gln missense NM_001407728.1:c.4114G>C NP_001394657.1:p.Glu1372Gln missense NM_001407729.1:c.4114G>C NP_001394658.1:p.Glu1372Gln missense NM_001407730.1:c.4114G>C NP_001394659.1:p.Glu1372Gln missense NM_001407731.1:c.4114G>C NP_001394660.1:p.Glu1372Gln missense NM_001407732.1:c.4114G>C NP_001394661.1:p.Glu1372Gln missense NM_001407733.1:c.4114G>C NP_001394662.1:p.Glu1372Gln missense NM_001407734.1:c.4114G>C NP_001394663.1:p.Glu1372Gln missense NM_001407735.1:c.4114G>C NP_001394664.1:p.Glu1372Gln missense NM_001407736.1:c.4114G>C NP_001394665.1:p.Glu1372Gln missense NM_001407737.1:c.4114G>C NP_001394666.1:p.Glu1372Gln missense NM_001407738.1:c.4114G>C NP_001394667.1:p.Glu1372Gln missense NM_001407739.1:c.4114G>C NP_001394668.1:p.Glu1372Gln missense NM_001407740.1:c.4111G>C NP_001394669.1:p.Glu1371Gln missense NM_001407741.1:c.4111G>C NP_001394670.1:p.Glu1371Gln missense NM_001407742.1:c.4111G>C NP_001394671.1:p.Glu1371Gln missense NM_001407743.1:c.4111G>C NP_001394672.1:p.Glu1371Gln missense NM_001407744.1:c.4111G>C NP_001394673.1:p.Glu1371Gln missense NM_001407745.1:c.4111G>C NP_001394674.1:p.Glu1371Gln missense NM_001407746.1:c.4111G>C NP_001394675.1:p.Glu1371Gln missense NM_001407747.1:c.4111G>C NP_001394676.1:p.Glu1371Gln missense NM_001407748.1:c.4111G>C NP_001394677.1:p.Glu1371Gln missense NM_001407749.1:c.4111G>C NP_001394678.1:p.Glu1371Gln missense NM_001407750.1:c.4111G>C NP_001394679.1:p.Glu1371Gln missense NM_001407751.1:c.4111G>C NP_001394680.1:p.Glu1371Gln missense NM_001407752.1:c.4111G>C NP_001394681.1:p.Glu1371Gln missense NM_001407838.1:c.4111G>C NP_001394767.1:p.Glu1371Gln missense NM_001407839.1:c.4111G>C NP_001394768.1:p.Glu1371Gln missense NM_001407841.1:c.4111G>C NP_001394770.1:p.Glu1371Gln missense NM_001407842.1:c.4111G>C NP_001394771.1:p.Glu1371Gln missense NM_001407843.1:c.4111G>C NP_001394772.1:p.Glu1371Gln missense NM_001407844.1:c.4111G>C NP_001394773.1:p.Glu1371Gln missense NM_001407845.1:c.4111G>C NP_001394774.1:p.Glu1371Gln missense NM_001407846.1:c.4111G>C NP_001394775.1:p.Glu1371Gln missense NM_001407847.1:c.4108G>C NP_001394776.1:p.Glu1370Gln missense NM_001407848.1:c.4108G>C NP_001394777.1:p.Glu1370Gln missense NM_001407849.1:c.4108G>C NP_001394778.1:p.Glu1370Gln missense NM_001407850.1:c.4111G>C NP_001394779.1:p.Glu1371Gln missense NM_001407851.1:c.4111G>C NP_001394780.1:p.Glu1371Gln missense NM_001407852.1:c.4111G>C NP_001394781.1:p.Glu1371Gln missense NM_001407853.1:c.4042G>C NP_001394782.1:p.Glu1348Gln missense NM_001407854.1:c.4255G>C NP_001394783.1:p.Glu1419Gln missense NM_001407858.1:c.4255G>C NP_001394787.1:p.Glu1419Gln missense NM_001407859.1:c.4255G>C NP_001394788.1:p.Glu1419Gln missense NM_001407860.1:c.4252G>C NP_001394789.1:p.Glu1418Gln missense NM_001407861.1:c.4252G>C NP_001394790.1:p.Glu1418Gln missense NM_001407862.1:c.4054G>C NP_001394791.1:p.Glu1352Gln missense NM_001407863.1:c.4132G>C NP_001394792.1:p.Glu1378Gln missense NM_001407874.1:c.4051G>C NP_001394803.1:p.Glu1351Gln missense NM_001407875.1:c.4051G>C NP_001394804.1:p.Glu1351Gln missense NM_001407879.1:c.4045G>C NP_001394808.1:p.Glu1349Gln missense NM_001407881.1:c.4045G>C NP_001394810.1:p.Glu1349Gln missense NM_001407882.1:c.4045G>C NP_001394811.1:p.Glu1349Gln missense NM_001407884.1:c.4045G>C NP_001394813.1:p.Glu1349Gln missense NM_001407885.1:c.4045G>C NP_001394814.1:p.Glu1349Gln missense NM_001407886.1:c.4045G>C NP_001394815.1:p.Glu1349Gln missense NM_001407887.1:c.4045G>C NP_001394816.1:p.Glu1349Gln missense NM_001407889.1:c.4045G>C NP_001394818.1:p.Glu1349Gln missense NM_001407894.1:c.4042G>C NP_001394823.1:p.Glu1348Gln missense NM_001407895.1:c.4042G>C NP_001394824.1:p.Glu1348Gln missense NM_001407896.1:c.4042G>C NP_001394825.1:p.Glu1348Gln missense NM_001407897.1:c.4042G>C NP_001394826.1:p.Glu1348Gln missense NM_001407898.1:c.4042G>C NP_001394827.1:p.Glu1348Gln missense NM_001407899.1:c.4042G>C NP_001394828.1:p.Glu1348Gln missense NM_001407900.1:c.4045G>C NP_001394829.1:p.Glu1349Gln missense NM_001407902.1:c.4045G>C NP_001394831.1:p.Glu1349Gln missense NM_001407904.1:c.4045G>C NP_001394833.1:p.Glu1349Gln missense NM_001407906.1:c.4045G>C NP_001394835.1:p.Glu1349Gln missense NM_001407907.1:c.4042G>C NP_001394836.1:p.Glu1348Gln missense NM_001407908.1:c.4042G>C NP_001394837.1:p.Glu1348Gln missense NM_001407909.1:c.4042G>C NP_001394838.1:p.Glu1348Gln missense NM_001407910.1:c.4042G>C NP_001394839.1:p.Glu1348Gln missense NM_001407915.1:c.4039G>C NP_001394844.1:p.Glu1347Gln missense NM_001407916.1:c.4042G>C NP_001394845.1:p.Glu1348Gln missense NM_001407917.1:c.4042G>C NP_001394846.1:p.Glu1348Gln missense NM_001407918.1:c.4042G>C NP_001394847.1:p.Glu1348Gln missense NM_001407919.1:c.4132G>C NP_001394848.1:p.Glu1378Gln missense NM_001407920.1:c.3991G>C NP_001394849.1:p.Glu1331Gln missense NM_001407921.1:c.3991G>C NP_001394850.1:p.Glu1331Gln missense NM_001407922.1:c.3991G>C NP_001394851.1:p.Glu1331Gln missense NM_001407923.1:c.3991G>C NP_001394852.1:p.Glu1331Gln missense NM_001407924.1:c.3991G>C NP_001394853.1:p.Glu1331Gln missense NM_001407925.1:c.3991G>C NP_001394854.1:p.Glu1331Gln missense NM_001407926.1:c.3991G>C NP_001394855.1:p.Glu1331Gln missense NM_001407927.1:c.3991G>C NP_001394856.1:p.Glu1331Gln missense NM_001407928.1:c.3991G>C NP_001394857.1:p.Glu1331Gln missense NM_001407929.1:c.3991G>C NP_001394858.1:p.Glu1331Gln missense NM_001407930.1:c.3988G>C NP_001394859.1:p.Glu1330Gln missense NM_001407931.1:c.3988G>C NP_001394860.1:p.Glu1330Gln missense NM_001407932.1:c.3988G>C NP_001394861.1:p.Glu1330Gln missense NM_001407933.1:c.3988G>C NP_001394862.1:p.Glu1330Gln missense NM_001407934.1:c.3985G>C NP_001394863.1:p.Glu1329Gln missense NM_001407935.1:c.3988G>C NP_001394864.1:p.Glu1330Gln missense NM_001407936.1:c.3988G>C NP_001394865.1:p.Glu1330Gln missense NM_001407937.1:c.4132G>C NP_001394866.1:p.Glu1378Gln missense NM_001407938.1:c.4132G>C NP_001394867.1:p.Glu1378Gln missense NM_001407939.1:c.4132G>C NP_001394868.1:p.Glu1378Gln missense NM_001407940.1:c.4129G>C NP_001394869.1:p.Glu1377Gln missense NM_001407941.1:c.4129G>C NP_001394870.1:p.Glu1377Gln missense NM_001407942.1:c.4114G>C NP_001394871.1:p.Glu1372Gln missense NM_001407943.1:c.4111G>C NP_001394872.1:p.Glu1371Gln missense NM_001407944.1:c.4114G>C NP_001394873.1:p.Glu1372Gln missense NM_001407945.1:c.4114G>C NP_001394874.1:p.Glu1372Gln missense NM_001407946.1:c.3922G>C NP_001394875.1:p.Glu1308Gln missense NM_001407947.1:c.3922G>C NP_001394876.1:p.Glu1308Gln missense NM_001407948.1:c.3922G>C NP_001394877.1:p.Glu1308Gln missense NM_001407949.1:c.3922G>C NP_001394878.1:p.Glu1308Gln missense NM_001407950.1:c.3922G>C NP_001394879.1:p.Glu1308Gln missense NM_001407951.1:c.3922G>C NP_001394880.1:p.Glu1308Gln missense NM_001407952.1:c.3919G>C NP_001394881.1:p.Glu1307Gln missense NM_001407953.1:c.3919G>C NP_001394882.1:p.Glu1307Gln missense NM_001407954.1:c.3919G>C NP_001394883.1:p.Glu1307Gln missense NM_001407955.1:c.3919G>C NP_001394884.1:p.Glu1307Gln missense NM_001407956.1:c.3916G>C NP_001394885.1:p.Glu1306Gln missense NM_001407957.1:c.3919G>C NP_001394886.1:p.Glu1307Gln missense NM_001407958.1:c.3919G>C NP_001394887.1:p.Glu1307Gln missense NM_001407959.1:c.3874G>C NP_001394888.1:p.Glu1292Gln missense NM_001407960.1:c.3874G>C NP_001394889.1:p.Glu1292Gln missense NM_001407962.1:c.3871G>C NP_001394891.1:p.Glu1291Gln missense NM_001407963.1:c.3871G>C NP_001394892.1:p.Glu1291Gln missense NM_001407964.1:c.4111G>C NP_001394893.1:p.Glu1371Gln missense NM_001407965.1:c.3748G>C NP_001394894.1:p.Glu1250Gln missense NM_001407966.1:c.3367G>C NP_001394895.1:p.Glu1123Gln missense NM_001407967.1:c.3367G>C NP_001394896.1:p.Glu1123Gln missense NM_001407968.1:c.1651G>C NP_001394897.1:p.Glu551Gln missense NM_001407969.1:c.1648G>C NP_001394898.1:p.Glu550Gln missense NM_001407970.1:c.946G>C NP_001394899.1:p.Glu316Gln missense NM_001407971.1:c.946G>C NP_001394900.1:p.Glu316Gln missense NM_001407972.1:c.943G>C NP_001394901.1:p.Glu315Gln missense NM_001407973.1:c.946G>C NP_001394902.1:p.Glu316Gln missense NM_001407974.1:c.946G>C NP_001394903.1:p.Glu316Gln missense NM_001407975.1:c.946G>C NP_001394904.1:p.Glu316Gln missense NM_001407976.1:c.946G>C NP_001394905.1:p.Glu316Gln missense NM_001407977.1:c.946G>C NP_001394906.1:p.Glu316Gln missense NM_001407978.1:c.946G>C NP_001394907.1:p.Glu316Gln missense NM_001407979.1:c.943G>C NP_001394908.1:p.Glu315Gln missense NM_001407980.1:c.943G>C NP_001394909.1:p.Glu315Gln missense NM_001407981.1:c.943G>C NP_001394910.1:p.Glu315Gln missense NM_001407982.1:c.943G>C NP_001394911.1:p.Glu315Gln missense NM_001407983.1:c.943G>C NP_001394912.1:p.Glu315Gln missense NM_001407984.1:c.943G>C NP_001394913.1:p.Glu315Gln missense NM_001407985.1:c.943G>C NP_001394914.1:p.Glu315Gln missense NM_001407986.1:c.943G>C NP_001394915.1:p.Glu315Gln missense NM_001407990.1:c.943G>C NP_001394919.1:p.Glu315Gln missense NM_001407991.1:c.943G>C NP_001394920.1:p.Glu315Gln missense NM_001407992.1:c.943G>C NP_001394921.1:p.Glu315Gln missense NM_001407993.1:c.946G>C NP_001394922.1:p.Glu316Gln missense NM_001408392.1:c.943G>C NP_001395321.1:p.Glu315Gln missense NM_001408396.1:c.943G>C NP_001395325.1:p.Glu315Gln missense NM_001408397.1:c.943G>C NP_001395326.1:p.Glu315Gln missense NM_001408398.1:c.943G>C NP_001395327.1:p.Glu315Gln missense NM_001408399.1:c.943G>C NP_001395328.1:p.Glu315Gln missense NM_001408400.1:c.940G>C NP_001395329.1:p.Glu314Gln missense NM_001408401.1:c.940G>C NP_001395330.1:p.Glu314Gln missense NM_001408402.1:c.940G>C NP_001395331.1:p.Glu314Gln missense NM_001408403.1:c.943G>C NP_001395332.1:p.Glu315Gln missense NM_001408404.1:c.943G>C NP_001395333.1:p.Glu315Gln missense NM_001408406.1:c.937G>C NP_001395335.1:p.Glu313Gln missense NM_001408407.1:c.940G>C NP_001395336.1:p.Glu314Gln missense NM_001408408.1:c.937G>C NP_001395337.1:p.Glu313Gln missense NM_001408409.1:c.868G>C NP_001395338.1:p.Glu290Gln missense NM_001408410.1:c.805G>C NP_001395339.1:p.Glu269Gln missense NM_001408411.1:c.868G>C NP_001395340.1:p.Glu290Gln missense NM_001408412.1:c.868G>C NP_001395341.1:p.Glu290Gln missense NM_001408413.1:c.865G>C NP_001395342.1:p.Glu289Gln missense NM_001408414.1:c.868G>C NP_001395343.1:p.Glu290Gln missense NM_001408415.1:c.868G>C NP_001395344.1:p.Glu290Gln missense NM_001408416.1:c.865G>C NP_001395345.1:p.Glu289Gln missense NM_001408418.1:c.829G>C NP_001395347.1:p.Glu277Gln missense NM_001408419.1:c.829G>C NP_001395348.1:p.Glu277Gln missense NM_001408420.1:c.829G>C NP_001395349.1:p.Glu277Gln missense NM_001408421.1:c.826G>C NP_001395350.1:p.Glu276Gln missense NM_001408422.1:c.829G>C NP_001395351.1:p.Glu277Gln missense NM_001408423.1:c.829G>C NP_001395352.1:p.Glu277Gln missense NM_001408424.1:c.826G>C NP_001395353.1:p.Glu276Gln missense NM_001408425.1:c.823G>C NP_001395354.1:p.Glu275Gln missense NM_001408426.1:c.823G>C NP_001395355.1:p.Glu275Gln missense NM_001408427.1:c.823G>C NP_001395356.1:p.Glu275Gln missense NM_001408428.1:c.823G>C NP_001395357.1:p.Glu275Gln missense NM_001408429.1:c.823G>C NP_001395358.1:p.Glu275Gln missense NM_001408430.1:c.823G>C NP_001395359.1:p.Glu275Gln missense NM_001408431.1:c.826G>C NP_001395360.1:p.Glu276Gln missense NM_001408432.1:c.820G>C NP_001395361.1:p.Glu274Gln missense NM_001408433.1:c.820G>C NP_001395362.1:p.Glu274Gln missense NM_001408434.1:c.820G>C NP_001395363.1:p.Glu274Gln missense NM_001408435.1:c.820G>C NP_001395364.1:p.Glu274Gln missense NM_001408436.1:c.823G>C NP_001395365.1:p.Glu275Gln missense NM_001408437.1:c.823G>C NP_001395366.1:p.Glu275Gln missense NM_001408438.1:c.823G>C NP_001395367.1:p.Glu275Gln missense NM_001408439.1:c.823G>C NP_001395368.1:p.Glu275Gln missense NM_001408440.1:c.823G>C NP_001395369.1:p.Glu275Gln missense NM_001408441.1:c.820G>C NP_001395370.1:p.Glu274Gln missense NM_001408442.1:c.820G>C NP_001395371.1:p.Glu274Gln missense NM_001408443.1:c.820G>C NP_001395372.1:p.Glu274Gln missense NM_001408444.1:c.820G>C NP_001395373.1:p.Glu274Gln missense NM_001408445.1:c.820G>C NP_001395374.1:p.Glu274Gln missense NM_001408446.1:c.820G>C NP_001395375.1:p.Glu274Gln missense NM_001408447.1:c.820G>C NP_001395376.1:p.Glu274Gln missense NM_001408448.1:c.820G>C NP_001395377.1:p.Glu274Gln missense NM_001408450.1:c.820G>C NP_001395379.1:p.Glu274Gln missense NM_001408451.1:c.811G>C NP_001395380.1:p.Glu271Gln missense NM_001408452.1:c.805G>C NP_001395381.1:p.Glu269Gln missense NM_001408453.1:c.805G>C NP_001395382.1:p.Glu269Gln missense NM_001408454.1:c.805G>C NP_001395383.1:p.Glu269Gln missense NM_001408455.1:c.805G>C NP_001395384.1:p.Glu269Gln missense NM_001408456.1:c.805G>C NP_001395385.1:p.Glu269Gln missense NM_001408457.1:c.805G>C NP_001395386.1:p.Glu269Gln missense NM_001408458.1:c.805G>C NP_001395387.1:p.Glu269Gln missense NM_001408459.1:c.805G>C NP_001395388.1:p.Glu269Gln missense NM_001408460.1:c.805G>C NP_001395389.1:p.Glu269Gln missense NM_001408461.1:c.805G>C NP_001395390.1:p.Glu269Gln missense NM_001408462.1:c.802G>C NP_001395391.1:p.Glu268Gln missense NM_001408463.1:c.802G>C NP_001395392.1:p.Glu268Gln missense NM_001408464.1:c.802G>C NP_001395393.1:p.Glu268Gln missense NM_001408465.1:c.802G>C NP_001395394.1:p.Glu268Gln missense NM_001408466.1:c.802G>C NP_001395395.1:p.Glu268Gln missense NM_001408467.1:c.802G>C NP_001395396.1:p.Glu268Gln missense NM_001408468.1:c.802G>C NP_001395397.1:p.Glu268Gln missense NM_001408469.1:c.802G>C NP_001395398.1:p.Glu268Gln missense NM_001408470.1:c.799G>C NP_001395399.1:p.Glu267Gln missense NM_001408472.1:c.943G>C NP_001395401.1:p.Glu315Gln missense NM_001408473.1:c.943G>C NP_001395402.1:p.Glu315Gln missense NM_001408474.1:c.745G>C NP_001395403.1:p.Glu249Gln missense NM_001408475.1:c.742G>C NP_001395404.1:p.Glu248Gln missense NM_001408476.1:c.745G>C NP_001395405.1:p.Glu249Gln missense NM_001408478.1:c.736G>C NP_001395407.1:p.Glu246Gln missense NM_001408479.1:c.736G>C NP_001395408.1:p.Glu246Gln missense NM_001408480.1:c.736G>C NP_001395409.1:p.Glu246Gln missense NM_001408481.1:c.736G>C NP_001395410.1:p.Glu246Gln missense NM_001408482.1:c.736G>C NP_001395411.1:p.Glu246Gln missense NM_001408483.1:c.736G>C NP_001395412.1:p.Glu246Gln missense NM_001408484.1:c.736G>C NP_001395413.1:p.Glu246Gln missense NM_001408485.1:c.736G>C NP_001395414.1:p.Glu246Gln missense NM_001408489.1:c.733G>C NP_001395418.1:p.Glu245Gln missense NM_001408490.1:c.733G>C NP_001395419.1:p.Glu245Gln missense NM_001408491.1:c.733G>C NP_001395420.1:p.Glu245Gln missense NM_001408492.1:c.733G>C NP_001395421.1:p.Glu245Gln missense NM_001408493.1:c.733G>C NP_001395422.1:p.Glu245Gln missense NM_001408494.1:c.706G>C NP_001395423.1:p.Glu236Gln missense NM_001408495.1:c.703G>C NP_001395424.1:p.Glu235Gln missense NM_001408496.1:c.682G>C NP_001395425.1:p.Glu228Gln missense NM_001408497.1:c.682G>C NP_001395426.1:p.Glu228Gln missense NM_001408498.1:c.682G>C NP_001395427.1:p.Glu228Gln missense NM_001408499.1:c.682G>C NP_001395428.1:p.Glu228Gln missense NM_001408500.1:c.682G>C NP_001395429.1:p.Glu228Gln missense NM_001408501.1:c.682G>C NP_001395430.1:p.Glu228Gln missense NM_001408502.1:c.613G>C NP_001395431.1:p.Glu205Gln missense NM_001408503.1:c.679G>C NP_001395432.1:p.Glu227Gln missense NM_001408504.1:c.679G>C NP_001395433.1:p.Glu227Gln missense NM_001408505.1:c.679G>C NP_001395434.1:p.Glu227Gln missense NM_001408506.1:c.619G>C NP_001395435.1:p.Glu207Gln missense NM_001408507.1:c.616G>C NP_001395436.1:p.Glu206Gln missense NM_001408508.1:c.607G>C NP_001395437.1:p.Glu203Gln missense NM_001408509.1:c.607G>C NP_001395438.1:p.Glu203Gln missense NM_001408510.1:c.565G>C NP_001395439.1:p.Glu189Gln missense NM_001408511.1:c.562G>C NP_001395440.1:p.Glu188Gln missense NM_001408512.1:c.442G>C NP_001395441.1:p.Glu148Gln missense NM_001408513.1:c.733G>C NP_001395442.1:p.Glu245Gln missense NM_001408514.1:c.736G>C NP_001395443.1:p.Glu246Gln missense NM_007297.4:c.4114G>C NP_009228.2:p.Glu1372Gln missense NM_007298.4:c.946G>C NP_009229.2:p.Glu316Gln missense NM_007299.4:c.946G>C NP_009230.2:p.Glu316Gln missense NM_007300.4:c.4255G>C NP_009231.2:p.Glu1419Gln missense NM_007304.2:c.946G>C NP_009235.2:p.Glu316Gln missense NR_027676.2:n.4432G>C non-coding transcript variant NC_000017.11:g.43082506C>G NC_000017.10:g.41234523C>G NG_005905.2:g.135478G>C LRG_292:g.135478G>C LRG_292t1:c.4255G>C LRG_292p1:p.Glu1419Gln U14680.1:n.4374G>C - Protein change
- E1419Q, E316Q, E1372Q, E1329Q, E1347Q, E1378Q, E206Q, E228Q, E235Q, E267Q, E315Q, E550Q, E1123Q, E1291Q, E1306Q, E1308Q, E1348Q, E1349Q, E1377Q, E1391Q, E1392Q, E189Q, E205Q, E248Q, E249Q, E271Q, E276Q, E290Q, E313Q, E314Q, E1307Q, E1330Q, E1370Q, E1418Q, E148Q, E236Q, E245Q, E277Q, E551Q, E1250Q, E1292Q, E1331Q, E1351Q, E1352Q, E1371Q, E1376Q, E1393Q, E1415Q, E1417Q, E188Q, E203Q, E207Q, E227Q, E246Q, E268Q, E269Q, E274Q, E275Q, E289Q
- Other names
-
4374G>C
- Canonical SPDI
- NC_000017.11:43082505:C:G
-
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.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00000
- 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. |
|---|---|---|---|---|
| Benign (4) |
reviewed by expert panel
|
Aug 10, 2015 | RCV000112305.14 | |
| Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 4, 2016 | RCV000162984.13 | |
| Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Mar 13, 2023 | RCV000588065.16 | |
| Likely benign (1) |
no assertion criteria provided
|
Aug 27, 2012 | RCV000735479.9 | |
| Likely benign (1) |
criteria provided, single submitter
|
Jan 4, 2024 | RCV001078624.14 |
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. |
|
|---|---|---|---|---|---|
|
Benign
(Aug 10, 2015)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000244357.1
First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015 |
Comment:
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on … (more)
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000152 (less)
|
|
|
Likely benign
(Jan 04, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000076516.10
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
|
|
|
Benign
(Nov 18, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000213472.6
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as 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)
|
|
|
Likely benign
(Mar 07, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699125.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The BRCA1 c.4255G>C (p.Glu1419Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign … (more)
Variant summary: The BRCA1 c.4255G>C (p.Glu1419Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121396 control chromosomes. However, multiple publications cite the variant with a classification of "likely neutral." In addition, multiple reputable databases/clinical laboratories cite the variant with a classification of "benign/likely benign/uncertain significance." In addition, a poster abstract (IUBMB 2015) cites a functional study that showed the variant to act comparable to wild type functions for transcriptional activation ability and PALB2 interaction. One recent functional study (Woods_2016) showed preserved transcriptional activity and no deleterious effects on the BRCA1-PALB2 protein-protein interaction in the presence of this variant. Taken together, this variant is classified as likely benign. (less)
|
|
|
Benign
(Mar 04, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000903861.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
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Likely benign
(May 20, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000293656.11
First in ClinVar: Jul 24, 2016 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 22949387, 18951461, 21120943, 22753008, 17924331, 21990134)
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Likely benign
(Mar 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001133579.4
First in ClinVar: Jan 05, 2020 Last updated: Jan 06, 2024 |
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Benign
(Oct 02, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004817687.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Number of individuals with the variant: 1
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Uncertain significance
(Nov 25, 2004)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145042.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
Ethnicity/Population group: Western European
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Likely benign
(Aug 27, 2012)
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no assertion criteria provided
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000863616.1 First in ClinVar: Dec 24, 2018 Last updated: Dec 24, 2018 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591501.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Glu1419Gln variant has been identified in 2/114310 proband chromosomes of individuals with breast cancer and/or ovarian cancer; although, no control chromosomes were tested to … (more)
The p.Glu1419Gln variant has been identified in 2/114310 proband chromosomes of individuals with breast cancer and/or ovarian cancer; although, no control chromosomes were tested to establish the variant's frequency in the general population (Caux-Moncoutier 2011, Judkins 2005a, Lindor 2011, Millot 2012). The variant is listed in dbSNP database (ID#:rs80357309) as coming from a "clinical source" but no frequency information was provided, and so the prevalence of this variant in the population is not known. The p.Glu1419 residue is conserved in mammals, but computational analyses (PolyPhen, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In addition, this variant is listed in the BIC (x1) database, as well as in the UMD mutation database to co-occur with a pathogenic mutation in BRCA2 c.3744_3747delTGAG (p.Ser1248ArgfsX10), increasing the likelihood that p.Glu1419Gln is benign. In summary, based on the above information, the p.Arg3370Arg variant is classified as predicted benign. (less)
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Comment:
Comment:
This alteration is classified as 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.
Comment:
Variant summary: The BRCA1 c.4255G>C (p.Glu1419Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121396 control chromosomes. However, multiple publications cite the variant with a classification of "likely neutral." In addition, multiple reputable databases/clinical laboratories cite the variant with a classification of "benign/likely benign/uncertain significance." In addition, a poster abstract (IUBMB 2015) cites a functional study that showed the variant to act comparable to wild type functions for transcriptional activation ability and PALB2 interaction. One recent functional study (Woods_2016) showed preserved transcriptional activity and no deleterious effects on the BRCA1-PALB2 protein-protein interaction in the presence of this variant. Taken together, this variant is classified as likely benign.
Comment:
This variant is associated with the following publications: (PMID: 22949387, 18951461, 21120943, 22753008, 17924331, 21990134)
Comment:
The p.Glu1419Gln variant has been identified in 2/114310 proband chromosomes of individuals with breast cancer and/or ovarian cancer; although, no control chromosomes were tested to establish the variant's frequency in the general population (Caux-Moncoutier 2011, Judkins 2005a, Lindor 2011, Millot 2012). The variant is listed in dbSNP database (ID#:rs80357309) as coming from a "clinical source" but no frequency information was provided, and so the prevalence of this variant in the population is not known. The p.Glu1419 residue is conserved in mammals, but computational analyses (PolyPhen, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In addition, this variant is listed in the BIC (x1) database, as well as in the UMD mutation database to co-occur with a pathogenic mutation in BRCA2 c.3744_3747delTGAG (p.Ser1248ArgfsX10), increasing the likelihood that p.Glu1419Gln is benign. In summary, based on the above information, the p.Arg3370Arg variant is classified as predicted benign.
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:
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000152
Comment:
This alteration is classified as 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.
Comment:
Variant summary: The BRCA1 c.4255G>C (p.Glu1419Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121396 control chromosomes. However, multiple publications cite the variant with a classification of "likely neutral." In addition, multiple reputable databases/clinical laboratories cite the variant with a classification of "benign/likely benign/uncertain significance." In addition, a poster abstract (IUBMB 2015) cites a functional study that showed the variant to act comparable to wild type functions for transcriptional activation ability and PALB2 interaction. One recent functional study (Woods_2016) showed preserved transcriptional activity and no deleterious effects on the BRCA1-PALB2 protein-protein interaction in the presence of this variant. Taken together, this variant is classified as likely benign.
Comment:
This variant is associated with the following publications: (PMID: 22949387, 18951461, 21120943, 22753008, 17924331, 21990134)
Comment:
The p.Glu1419Gln variant has been identified in 2/114310 proband chromosomes of individuals with breast cancer and/or ovarian cancer; although, no control chromosomes were tested to establish the variant's frequency in the general population (Caux-Moncoutier 2011, Judkins 2005a, Lindor 2011, Millot 2012). The variant is listed in dbSNP database (ID#:rs80357309) as coming from a "clinical source" but no frequency information was provided, and so the prevalence of this variant in the population is not known. The p.Glu1419 residue is conserved in mammals, but computational analyses (PolyPhen, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In addition, this variant is listed in the BIC (x1) database, as well as in the UMD mutation database to co-occur with a pathogenic mutation in BRCA2 c.3744_3747delTGAG (p.Ser1248ArgfsX10), increasing the likelihood that p.Glu1419Gln is benign. In summary, based on the above information, the p.Arg3370Arg variant is classified as predicted benign.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
| Integration of functional assay data results provides strong evidence for classification of hundreds of BRCA1 variants of uncertain significance. | Lyra PCM Jr | Genetics in medicine : official journal of the American College of Medical Genetics | 2021 | PMID: 33087888 |
| Prediction of the functional impact of missense variants in BRCA1 and BRCA2 with BRCA-ML. | Hart SN | NPJ breast cancer | 2020 | PMID: 32377563 |
| Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation. | Fernandes VC | The Journal of biological chemistry | 2019 | PMID: 30765603 |
| Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance. | Woods NT | NPJ genomic medicine | 2016 | PMID: 28781887 |
| Benchmarking mutation effect prediction algorithms using functionally validated cancer-related missense mutations. | Martelotto LG | Genome biology | 2014 | PMID: 25348012 |
| Missense variants of uncertain significance (VUS) altering the phosphorylation patterns of BRCA1 and BRCA2. | Tram E | PloS one | 2013 | PMID: 23704879 |
| A guide for functional analysis of BRCA1 variants of uncertain significance. | Millot GA | Human mutation | 2012 | PMID: 22753008 |
| 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 |
| EMMA, a cost- and time-effective diagnostic method for simultaneous detection of point mutations and large-scale genomic rearrangements: application to BRCA1 and BRCA2 in 1,525 patients. | Caux-Moncoutier V | Human mutation | 2011 | PMID: 21120943 |
| A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. | Easton DF | American journal of human genetics | 2007 | PMID: 17924331 |
| Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. | Judkins T | Cancer research | 2005 | PMID: 16267036 |
| The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
| http://hci-exlovd.hci.utah.edu/variants.php?select_db=BRCA1&action=search_all&search_Variant%2FDNA=c.4255G%3EC | - | - | - | - |
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Text-mined citations for rs80357309 ...
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 10, 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.