ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2942C>A (p.Pro981Gln)

dbSNP: rs876659025
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218628 SCV000274982 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-23 criteria provided, single submitter clinical testing The p.P981Q variant (also known as c.2942C>A), located in coding exon 9 of the BRCA1 gene, results from a C to A substitution at nucleotide position 2942. The proline at codon 981 is replaced by glutamine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and glutamine is the reference amino acid in other 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001218201 SCV001390073 uncertain significance Hereditary breast ovarian cancer syndrome 2024-12-12 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 981 of the BRCA1 protein (p.Pro981Gln). 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: 231209). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA1 protein function with a negative predictive value of 80%. 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 RCV000218628 SCV003849233 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).

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