Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000213551 | SCV000273552 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-01 | criteria provided, single submitter | clinical testing | The p.P64L variant (also known as c.191C>T), located in coding exon 4 of the SDHC gene, results from a C to T substitution at nucleotide position 191. The proline at codon 64 is replaced by leucine, 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. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003765403 | SCV004582600 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 64 of the SDHC protein (p.Pro64Leu). This variant is not present in population databases (gnomAD no frequency). 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: 230118). 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. |