ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4979C>T (p.Pro1660Leu)

dbSNP: rs397507345
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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 RCV000166270 SCV000217051 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-22 criteria provided, single submitter clinical testing The p.P1660L variant (also known as c.4979C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 4979. The proline at codon 1660 is replaced by leucine, an amino acid with similar properties. This amino acid position is poorly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001042145 SCV001205811 uncertain significance Hereditary breast ovarian cancer syndrome 2024-08-12 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1660 of the BRCA2 protein (p.Pro1660Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 37937). 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 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000166270 SCV003852256 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).
Sharing Clinical Reports Project (SCRP) RCV000031518 SCV000054123 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2008-10-14 no assertion criteria provided clinical testing

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