Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000543957 | SCV000641432 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2023-05-21 | 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 465967). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. This variant is present in population databases (rs761381438, gnomAD 0.007%). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 8 of the SDHC protein (p.His8Gln). |
| Ambry Genetics | RCV001015761 | SCV001176631 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-24 | criteria provided, single submitter | clinical testing | The p.H8Q variant (also known as c.24C>A), located in coding exon 2 of the SDHC gene, results from a C to A substitution at nucleotide position 24. The histidine at codon 8 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |