Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017121 | SCV001178152 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-08 | criteria provided, single submitter | clinical testing | The p.K35E variant (also known as c.103A>G), located in coding exon 3 of the SDHC gene, results from an A to G substitution at nucleotide position 103. The lysine at codon 35 is replaced by glutamic acid, an amino acid with 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. |
| Labcorp Genetics |
RCV001035296 | SCV001198620 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 35 of the SDHC protein (p.Lys35Glu). This variant is present in population databases (rs746315913, gnomAD 0.0008%). 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: 822072). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| All of Us Research Program, |
RCV004004564 | SCV004828943 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-06-28 | criteria provided, single submitter | clinical testing |