ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1343G>C (p.Arg448Pro)

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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 RCV002387761 SCV002693683 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-11 criteria provided, single submitter clinical testing The p.R448P variant (also known as c.1343G>C), located in coding exon 9 of the BRCA2 gene, results from a G to C substitution at nucleotide position 1343. The arginine at codon 448 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is conserved. 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 RCV003103654 SCV003288510 uncertain significance Hereditary breast ovarian cancer syndrome 2022-06-08 criteria provided, single submitter clinical testing 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. 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 BRCA2 protein function. This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 448 of the BRCA2 protein (p.Arg448Pro).
University of Washington Department of Laboratory Medicine, University of Washington RCV002387761 SCV003850019 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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