ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.1256G>A (p.Arg419Gln)

gnomAD frequency: 0.00001  dbSNP: rs748105919
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000463365 SCV000547235 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2023-10-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 419 of the BRIP1 protein (p.Arg419Gln). This variant is present in population databases (rs748105919, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 407792). 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. 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 RCV002418374 SCV002679083 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-23 criteria provided, single submitter clinical testing The p.R419Q variant (also known as c.1256G>A), located in coding exon 8 of the BRIP1 gene, results from a G to A substitution at nucleotide position 1256. The arginine at codon 419 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV004772921 SCV005386370 uncertain significance not provided 2024-01-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with duodenal carcinoma (PMID: 35171259); This variant is associated with the following publications: (PMID: 35171259)

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