ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.969C>G (p.His323Gln)

dbSNP: rs1555607775
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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 RCV001234117 SCV001406745 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2021-08-24 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. This sequence change replaces histidine with glutamine at codon 323 of the BRIP1 protein (p.His323Gln). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRIP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271633 SCV002555853 uncertain significance not specified 2022-06-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV002379893 SCV002694270 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-06 criteria provided, single submitter clinical testing The p.H323Q variant (also known as c.969C>G), located in coding exon 7 of the BRIP1 gene, results from a C to G substitution at nucleotide position 969. The histidine at codon 323 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and glutamine is the reference amino acid in other 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.

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