ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.520C>T (p.His174Tyr)

dbSNP: rs776248182
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000233677 SCV000291051 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2016-02-06 criteria provided, single submitter clinical testing This variant is present in population databases (rs776248182, ExAC 0.006%) and has been seen in an unaffected control individual in the literature (PMID: 26315354). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, this is a rare missense change with uncertain impact on protein function. There is no indication that this variant causes disease, but the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces histidine with tyrosine at codon 174 of the BRIP1 protein (p.His174Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine.
Ambry Genetics RCV002347915 SCV002646653 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-18 criteria provided, single submitter clinical testing The p.H174Y variant (also known as c.520C>T), located in coding exon 5 of the BRIP1 gene, results from a C to T substitution at nucleotide position 520. The histidine at codon 174 is replaced by tyrosine, an amino acid with similar properties. In one study, this alteration was observed in 0/3236 cases with invasive epithelial ovarian cancer and 1/3431 controls (Ramus SJ et al. J Natl Cancer Inst, 2015 Nov;107:). This amino acid position is 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.

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