ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5228G>C (p.Gly1743Ala)

dbSNP: rs1346819781
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589382 SCV000699223 uncertain significance not provided 2016-05-16 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.5228G>C (p.Gly1743Ala) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome (SNPs&GO not captured due to low reliability index). This variant is absent in 121412 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000822110 SCV000962896 uncertain significance Hereditary breast ovarian cancer syndrome 2021-10-25 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1743 of the BRCA1 protein (p.Gly1743Ala). This variant is not present in population databases (gnomAD no frequency). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BRCA1 function (PMID: 30209399). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 496391). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions.
Color Diagnostics, LLC DBA Color Health RCV001185322 SCV001351511 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-08 criteria provided, single submitter clinical testing This missense variant replaces glycine with alanine at codon 1743 of the BRCA1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. This variant has been reported to be intermediately functional in a haploid cell proliferation assay (PMID: 30209399) and functional but expressed at low levels in a transcriptional activation assay (PMID: 30765603). This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV000589382 SCV001815060 uncertain significance not provided 2019-12-24 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Also known as 5347G>C; This variant is associated with the following publications: (PMID: 30209399)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589382 SCV002046688 uncertain significance not provided 2021-03-09 criteria provided, single submitter clinical testing
Brotman Baty Institute, University of Washington RCV001075902 SCV001241554 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro

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