Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000799859 | SCV000939541 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2023-04-19 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 645715). 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with SDHC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 87 of the SDHC protein (p.Met87Val). |
All of Us Research Program, |
RCV004001630 | SCV004832896 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-04-10 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with valine at codon 87 of the SDHC 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 SDHC-related disorders 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 | RCV004949925 | SCV005500650 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-09 | criteria provided, single submitter | clinical testing | The p.M87V variant (also known as c.259A>G), located in coding exon 5 of the SDHC gene, results from an A to G substitution at nucleotide position 259. The methionine at codon 87 is replaced by valine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |