ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3392A>G (p.Asp1131Gly)

dbSNP: rs1555587813
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000534135 SCV000635894 uncertain significance Hereditary breast ovarian cancer syndrome 2022-02-20 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: 462608). This missense change has been observed in individual(s) with breast cancer (PMID: 32393398). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1131 of the BRCA1 protein (p.Asp1131Gly).
Molecular Endocrinology Laboratory, Christian Medical College RCV001770426 SCV002004023 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002469189 SCV002766357 uncertain significance not specified 2022-11-28 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3392A>G (p.Asp1131Gly) 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 allele was found at a frequency of 3.7e-06 in 273492 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3392A>G has been reported in the literature in at least one individual affected with Hereditary Breast And Ovarian Cancer Syndrome without strong evidence for causality (e.g. Sirisena_2020). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
University of Washington Department of Laboratory Medicine, University of Washington RCV003157702 SCV003850512 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

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