ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.736A>C (p.Ile246Leu)

dbSNP: rs376893571
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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 RCV001232376 SCV001404932 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2019-09-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with leucine at codon 246 of the BRIP1 protein (p.Ile246Leu). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and leucine. 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. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRIP1-related conditions. This variant is not present in population databases (ExAC no frequency).
Color Diagnostics, LLC DBA Color Health RCV001524495 SCV001734364 uncertain significance Hereditary cancer-predisposing syndrome 2020-05-26 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with leucine at codon 246 of the BRIP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001524495 SCV005553075 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-09 criteria provided, single submitter clinical testing The p.I246L variant (also known as c.736A>C), located in coding exon 6 of the BRIP1 gene, results from an A to C substitution at nucleotide position 736. The isoleucine at codon 246 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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