ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.1225A>G (p.Ser409Gly)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002364270 SCV002657928 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-28 criteria provided, single submitter clinical testing The p.S409G variant (also known as c.1225A>G), located in coding exon 8 of the BRIP1 gene, results from an A to G substitution at nucleotide position 1225. The serine at codon 409 is replaced by glycine, an amino acid with similar properties. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003103306 SCV003009476 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2024-05-28 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 409 of the BRIP1 protein (p.Ser409Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pancreatic ductal adenocarcinoma (PMID: 35171259). ClinVar contains an entry for this variant (Variation ID: 1754059). 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 BRIP1 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.

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