Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000414050 | SCV000491510 | likely pathogenic | not provided | 2016-06-20 | criteria provided, single submitter | clinical testing | The V276L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V276L variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The V276L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001290531 | SCV001478585 | uncertain significance | not specified | 2021-01-14 | criteria provided, single submitter | clinical testing | Variant summary: BRAF c.826G>C (p.Val276Leu) results in a conservative amino acid change located in the Protein kinase C-like, phorbol ester/diacylglycerol-binding domain (IPR002219) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251098 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.826G>C in individuals affected with Cardiofaciocutaneous Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic without evidence for independent evaluation. As a de-novo mode of inheritance has not been ruled out at our laboratory, based on the evidence outlined above, the variant was classified as uncertain significance. |