ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1963C>T (p.Pro655Ser) (rs753036322)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231802 SCV000290999 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-08-23 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 655 of the BRIP1 protein (p.Pro655Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs753036322, ExAC 0.002%). This variant has not been reported in the literature in individuals with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 241636). 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 disruptive, 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.
Ambry Genetics RCV000570087 SCV000661576 uncertain significance Hereditary cancer-predisposing syndrome 2016-12-12 criteria provided, single submitter clinical testing The p.P655S variant (also known as c.1963C>T), located in coding exon 13 of the BRIP1 gene, results from a C to T substitution at nucleotide position 1963. The proline at codon 655 is replaced by serine, an amino acid with 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.

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