ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4837A>T (p.Ser1613Cys) (rs1799966)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000589264 SCV000076686 likely benign not provided 2019-02-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130704 SCV000185591 likely benign Hereditary cancer-predisposing syndrome 2017-09-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene,Co-occurence with mutation in same gene (phase unknown),Intact protein function observed in appropriate functional assay(s)
GeneDx RCV000048673 SCV000209977 likely benign not specified 2017-05-12 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589264 SCV000605893 benign not provided 2019-04-18 criteria provided, single submitter clinical testing
Color RCV000130704 SCV000683220 likely benign Hereditary cancer-predisposing syndrome 2016-10-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589264 SCV000699177 uncertain significance not provided 2017-02-20 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.4837A>T (p.Ser1613Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a damaging outcome (SNPs&GO not captured due to low reliability index). This variant was found in 8/121360 control chromosomes at a frequency of 0.0000659, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). The variant has been reported in affected individuals in the literature, without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. However publications, and potentially databases, have mistakenly described the variant of interest as p.Ser1613Gly, which is an A>G nucleotide change and is present at a high frequency in the ExAC database (NV in GE). Therefore, caution must be taken when reviewing the literature. According to ClinVar, the variant of interest was reported in an individual affected with breast cancer (Invitae database). However, a pathogenic allele was also identified in the BRCA1 gene, which suggests that this c.4837A>T substitution was not the primary cause of disease in this individual. Two functional studies show contradictory results in regards to the effect of this variant on protein activity. Taken together, this variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Sharing Clinical Reports Project (SCRP) RCV000031194 SCV000053794 benign Breast-ovarian cancer, familial 1 2011-11-14 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031194 SCV000145194 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing

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