Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001202058 | SCV001373156 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2019-07-29 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with aspartic acid at codon 26 of the SDHC protein (p.Asn26Asp). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and aspartic acid. 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). |
| Ambry Genetics | RCV002402574 | SCV002668793 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-22 | criteria provided, single submitter | clinical testing | The p.N26D variant (also known as c.76A>G), located in coding exon 2 of the SDHC gene, results from an A to G substitution at nucleotide position 76. The asparagine at codon 26 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |