Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001346280 | SCV001540464 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 8 of the SDHC protein (p.His8Arg). This variant is present in population databases (rs776123707, gnomAD 0.006%). 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: 1042345). 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 arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
| Ambry Genetics | RCV002447417 | SCV002732018 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-22 | criteria provided, single submitter | clinical testing | The p.H8R variant (also known as c.23A>G), located in coding exon 2 of the SDHC gene, results from an A to G substitution at nucleotide position 23. The histidine at codon 8 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |