Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000690097 | SCV000817774 | uncertain significance | Renal cell carcinoma | 2021-03-26 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 806 of the MET protein (p.Val806Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant has been observed in a family affected with pheochromocytoma (PMID: 26700204). ClinVar contains an entry for this variant (Variation ID: 569466). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |
Gene |
RCV001584563 | SCV001819375 | uncertain significance | not provided | 2023-10-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in a case of familial pheochromocytoma (PMID: 26700204); This variant is associated with the following publications: (PMID: 26700204) |
Ambry Genetics | RCV002442439 | SCV002732827 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-03 | criteria provided, single submitter | clinical testing | The p.V806M variant (also known as c.2416G>A), located in coding exon 9 of the MET gene, results from a G to A substitution at nucleotide position 2416. The valine at codon 806 is replaced by methionine, an amino acid with highly similar properties. This alteration was detected in the exome of an index case of a three-generation kindred with non-syndromic pheochromocytomas (Toledo RA et al. Clin Cancer Res, 2016 05;22:2301-10). This amino acid position is highly 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. |
Baylor Genetics | RCV003465574 | SCV004192565 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 97 | 2023-06-27 | criteria provided, single submitter | clinical testing |