Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002421215 | SCV002721834 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-01-20 | criteria provided, single submitter | clinical testing | The p.S68P variant (also known as c.202T>C), located in coding exon 4 of the SDHC gene, results from a T to C substitution at nucleotide position 202. The serine at codon 68 is replaced by proline, an amino acid with similar properties. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with SDHC-related disease (Ambry internal data). In addition, this variant was reported in a 31-year-old female diagnosed with a paraganglioma who reported having a cousin diagnosed with a pheochromocytoma as a teenager (Daghlas S et al. BMJ Case Rep, 2021 Oct;14:). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on internal structural assessment, this alteration disrupts the ubiquinone binding site (Sun F et al. Cell, 2005 Jul;121:1043-57). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV003771762 | SCV004585243 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 68 of the SDHC protein (p.Ser68Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with paraganglioma (PMID: 34663632). ClinVar contains an entry for this variant (Variation ID: 1209920). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Genome Diagnostics Laboratory, |
RCV001579498 | SCV001807468 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
| Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001579498 | SCV001957270 | uncertain significance | not provided | no assertion criteria provided | clinical testing |