Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000814325 | SCV000954729 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2021-03-29 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SDHC-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 123 of the SDHC protein (p.Pro123Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. |
Ambry Genetics | RCV004949977 | SCV005500667 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-16 | criteria provided, single submitter | clinical testing | The p.P123L variant (also known as c.368C>T), located in coding exon 5 of the SDHC gene, results from a C to T substitution at nucleotide position 368. The proline at codon 123 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |