ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2342A>C (p.Glu781Ala) (rs587776482)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471903 SCV000549271 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-11-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with alanine at codon 781 of the BRCA1 protein (p.Glu781Ala). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 156186). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Ambry Genetics RCV000509839 SCV000608113 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-18 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000509839 SCV000909346 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781014 SCV000918766 uncertain significance not specified 2018-08-07 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2342A>C (p.Glu781Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245548 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2342A>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Sharing Clinical Reports Project (SCRP) RCV000144203 SCV000189276 uncertain significance Breast-ovarian cancer, familial 1 2011-02-17 no assertion criteria provided clinical testing

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