Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000794964 | SCV000934402 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2023-07-05 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SDHC protein function. 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. This variant disrupts the p.Arg50 amino acid residue in SDHC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19351833, 23666964, 24102379, 27279923). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 641671). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. This variant is present in population databases (rs769177037, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 50 of the SDHC protein (p.Arg50His). |
| Ambry Genetics | RCV002388432 | SCV002701431 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-26 | criteria provided, single submitter | clinical testing | The p.R50H variant (also known as c.149G>A), located in coding exon 3 of the SDHC gene, results from a G to A substitution at nucleotide position 149. The arginine at codon 50 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| All of Us Research Program, |
RCV004001593 | SCV004828435 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-11-30 | criteria provided, single submitter | clinical testing |