ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1837A>G (p.Arg613Gly) (rs863224753)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000195940 SCV000254958 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-06-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 613 of the BRCA1 protein (p.Arg613Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. This variant has not been published in the literature and is not present in population databases. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000220811 SCV000275529 uncertain significance Hereditary cancer-predisposing syndrome 2015-05-06 criteria provided, single submitter clinical testing
GeneDx RCV000484390 SCV000571683 uncertain significance not provided 2017-07-07 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.1837A>G at the cDNA level, p.Arg613Gly (R613G) at the protein level, and results in the change of an Arginine to a Glycine (AGG>GGG). Using alternate nomenclature, this variant would be defined as BRCA1 1956A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Arg613Gly was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Arginine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Arg613Gly occurs at a position that is not conserved and is located in the NLS2 motif and a region of interaction with multiple proteins (Borg 2010, Paul 2014). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Arg613Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000220811 SCV000909363 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-21 criteria provided, single submitter clinical testing

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