ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.3461G>C (p.Arg1154Thr) (rs1057522433)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000427270 SCV000527676 uncertain significance not provided 2016-05-05 criteria provided, single submitter clinical testing The R1154T variant in the BRIP1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R1154T variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. We interpret R1154T as a variant of uncertain significance.
Color RCV000775895 SCV000910379 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-24 criteria provided, single submitter clinical testing
Invitae RCV000820752 SCV000961479 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-09-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with threonine at codon 1154 of the BRIP1 protein (p.Arg1154Thr). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and threonine. 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 disease. ClinVar contains an entry for this variant (Variation ID: 386142). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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