ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1153C>A (p.Leu385Met) (rs748001678)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000582933 SCV000689252 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-07 criteria provided, single submitter clinical testing
GeneDx RCV000286010 SCV000329155 uncertain significance not provided 2018-08-16 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.1153C>A at the cDNA level, p.Leu385Met (L385M) at the protein level, and results in the change of a Leucine to a Methionine (CTG>ATG). This variant has been observed in at least one patient with breast cancer (Weber-Lassalle 2018). BRIP1 Leu385Met was not observed in large population cohorts (Lek 2016). This variant is located in the Helicase domain II (Cantor 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRIP1 Leu385Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000199172 SCV000255143 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces leucine with methionine at codon 385 of the BRIP1 protein (p.Leu385Met). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and methionine. 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: 216783). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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