ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1924G>C (p.Asp642His) (rs80357344)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000111734 SCV000244310 benign Breast-ovarian cancer, familial 1 2015-08-10 reviewed by expert panel curation 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 = 0.000014
Invitae RCV000047642 SCV000075655 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-02-19 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 642 of the BRCA1 protein (p.Asp642His). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 54401). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). However, based on multifactorial likelihood algorithms using genetic and in silico data, this variant has been determined to have a low probability of being pathogenic (PMID: 17924331, 21990134). In summary, this variant has uncertain impact on BRCA1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000162974 SCV000213462 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
GeneDx RCV000430192 SCV000518067 likely benign not specified 2015-07-07 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.
PreventionGenetics,PreventionGenetics RCV000679686 SCV000806904 likely benign not provided 2017-07-06 criteria provided, single submitter clinical testing
Color RCV000162974 SCV000906650 likely benign Hereditary cancer-predisposing syndrome 2017-12-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679686 SCV001133505 likely benign not provided 2018-11-03 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000111734 SCV000144250 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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