ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3992A>G (p.Gln1331Arg)

dbSNP: rs1060502363
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000467046 SCV000549413 uncertain significance Hereditary breast ovarian cancer syndrome 2022-01-23 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 1331 of the BRCA1 protein (p.Gln1331Arg). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 21318380). ClinVar contains an entry for this variant (Variation ID: 409366). 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. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003157522 SCV003849199 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).
Ambry Genetics RCV003157522 SCV005547451 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-20 criteria provided, single submitter clinical testing The p.Q1331R variant (also known as c.3992A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 3992. The glutamine at codon 1331 is replaced by arginine, an amino acid with highly similar properties. This alteration has been reported in an unaffected individual with a family history of breast cancer (Hansen TV et al. Fam Cancer, 2011 Jun;10:207-12). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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