Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002459100 | SCV002615905 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-11 | criteria provided, single submitter | clinical testing | The p.K117Q variant (also known as c.349A>C), located in coding exon 5 of the SDHC gene, results from an A to C substitution at nucleotide position 349. The lysine at codon 117 is replaced by glutamine, an amino acid with similar properties. This amino acid position is conserved. 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. |
| Labcorp Genetics |
RCV003775644 | SCV004610192 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 117 of the SDHC protein (p.Lys117Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1732014). 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 with a positive predictive value of 80%. 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. |