ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1199T>C (p.Leu400Pro)

dbSNP: rs397507264
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000229646 SCV000283165 uncertain significance Hereditary breast ovarian cancer syndrome 2024-02-08 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 400 of the BRCA2 protein (p.Leu400Pro). 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: 37729). 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.
Ambry Genetics RCV000571637 SCV000665955 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-16 criteria provided, single submitter clinical testing The p.L400P variant (also known as c.1199T>C), located in coding exon 9 of the BRCA2 gene, results from a T to C substitution at nucleotide position 1199. The leucine at codon 400 is replaced by proline, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6488 samples (12976 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0007% (greater than 300000 alleles tested) in our clinical cohort. This amino acid position is not well 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000571637 SCV003849904 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) RCV000031310 SCV000053915 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2007-03-09 no assertion criteria provided clinical testing

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