ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1471C>G (p.Gln491Glu)

dbSNP: rs62625303
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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 RCV000569954 SCV000665820 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-15 criteria provided, single submitter clinical testing The p.Q491E variant (also known as c.1471C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 1471. The glutamine at codon 491 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000569954 SCV001353800 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-16 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000569954 SCV003851274 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).
Labcorp Genetics (formerly Invitae), Labcorp RCV005091338 SCV005737803 uncertain significance Hereditary breast ovarian cancer syndrome 2024-03-17 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 491 of the BRCA1 protein (p.Gln491Glu). This variant is not present in population databases (gnomAD no frequency). 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: 481431). 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.

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