Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000560999 | SCV000664751 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-17 | criteria provided, single submitter | clinical testing | The p.Q21E variant (also known as c.61C>G), located in coding exon 2 of the SDHC gene, results from a C to G substitution at nucleotide position 61. The glutamine at codon 21 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is not 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. |
| Labcorp Genetics |
RCV000641909 | SCV000763559 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2022-12-04 | 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. ClinVar contains an entry for this variant (Variation ID: 480864). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 21 of the SDHC protein (p.Gln21Glu). |
| All of Us Research Program, |
RCV004000903 | SCV004817964 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-03-04 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004773006 | SCV005385179 | uncertain significance | not provided | 2024-01-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |