Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001299212 | SCV001488291 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2020-10-29 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SDHC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with aspartic acid at codon 12 of the SDHC protein (p.His12Asp). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and aspartic acid. |
| Ambry Genetics | RCV003373104 | SCV004096814 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-08 | criteria provided, single submitter | clinical testing | The p.H12D variant (also known as c.34C>G), located in coding exon 2 of the SDHC gene, results from a C to G substitution at nucleotide position 34. The histidine at codon 12 is replaced by aspartic acid, 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. |