ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.1739C>T (p.Ser580Leu)

dbSNP: rs1356014648
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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 RCV000551078 SCV000633569 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2022-02-18 criteria provided, single submitter clinical testing 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 461081). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 580 of the BRIP1 protein (p.Ser580Leu).
Ambry Genetics RCV001012933 SCV001173454 uncertain significance Hereditary cancer-predisposing syndrome 2020-08-29 criteria provided, single submitter clinical testing The p.S580L variant (also known as c.1739C>T), located in coding exon 11 of the BRIP1 gene, results from a C to T substitution at nucleotide position 1739. The serine at codon 580 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not 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.
Color Diagnostics, LLC DBA Color Health RCV001012933 SCV001357577 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-27 criteria provided, single submitter clinical testing This missense variant replaces serine with leucine at codon 580 of the BRIP1 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251448 chromosomes 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.

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