ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2500G>C (p.Gly834Arg) (rs786202215)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164931 SCV000215620 likely benign Hereditary cancer-predisposing syndrome 2017-12-11 criteria provided, single submitter clinical testing Other strong data supporting benign classification;In silico models in agreement (benign)
Integrated Genetics/Laboratory Corporation of America RCV000590464 SCV000698963 uncertain significance not provided 2017-02-09 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2500G>C (p.Gly834Arg) variant involves the alteration of a non-conserved nucleotide and is predicted to be benign by 3/4 in silico tools (SNPs&GO not captured due to low reliability index). The variant is located outside of some commonly known domains in BRCA1 protein (InterPro, UniPro). This variant is absent in 121354 control chromosomes from ExAC. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases, nor evaluated for functional impact by in vivo/vitro studies. A clinical diagnostic laboratory has reported this variant once in an individual undergoing BRCA1/2 testing without evidence to independently evaluate and has classified the variant as uncertain significance. Based on the currently available information, this variant is classified as a variant of uncertain significance (VUS).
Invitae RCV000695556 SCV000824065 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-06-26 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 834 of the BRCA1 protein (p.Gly834Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. 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 disease. ClinVar contains an entry for this variant (Variation ID: 185491). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Color RCV000164931 SCV001340806 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-16 criteria provided, single submitter clinical testing

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