ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3938A>G (p.Gln1313Arg)

dbSNP: rs765729710
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000707493 SCV000836593 uncertain significance Hereditary breast ovarian cancer syndrome 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1313 of the BRCA1 protein (p.Gln1313Arg). This variant is present in population databases (rs765729710, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 440470). 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 with a negative predictive value of 95%. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759530 SCV000888904 uncertain significance not provided 2018-02-06 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001524538 SCV001734427 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-26 criteria provided, single submitter clinical testing This missense variant replaces glutamine with arginine at codon 1313 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251228 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The 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 RCV000759530 SCV002601549 uncertain significance not provided 2022-05-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 4057A>G; This variant is associated with the following publications: (PMID: 15343273, 22737296)
Ambry Genetics RCV001524538 SCV002625144 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-29 criteria provided, single submitter clinical testing The p.Q1313R variant (also known as c.3938A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 3938. The glutamine at codon 1313 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV001524538 SCV003847677 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).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.