Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001022642 | SCV001184402 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-02-25 | criteria provided, single submitter | clinical testing | The p.S151Y variant (also known as c.452C>A), located in coding exon 6 of the SDHC gene, results from a C to A substitution at nucleotide position 452. The serine at codon 151 is replaced by tyrosine, an amino acid with dissimilar properties. This variant has been detected in multiple individuals with a paraganglioma (Ambry internal data). Based on internal structural analysis, the variant disrupts a region of SDHC near key binding sites (Zhou Q et al. Protein Cell, 2011 Jul;2:531-42). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). 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 |
RCV001862225 | SCV002196570 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2022-09-07 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 824974). This missense change has been observed in individual(s) with paraganglioma (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 151 of the SDHC protein (p.Ser151Tyr). |
| All of Us Research Program, |
RCV004004628 | SCV004829913 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-11-30 | criteria provided, single submitter | clinical testing |