Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001898711 | SCV002173675 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2022-11-13 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1403117). This missense change has been observed in individual(s) with head and neck paraganglioma (PMID: 19351833). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 58 of the SDHC protein (p.Ile58Thr). 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. Experimental studies have shown that this missense change does not substantially affect SDHC function (PMID: 23175444). 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: "Probably Damaging"; Align-GVGD: "Class C0"). |
| Ambry Genetics | RCV003303349 | SCV004000442 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-03 | criteria provided, single submitter | clinical testing | The p.I58T variant (also known as c.173T>C), located in coding exon 3 of the SDHC gene, results from a T to C substitution at nucleotide position 173. The isoleucine at codon 58 is replaced by threonine, an amino acid with similar properties. In a study of 598 unrelated probands diagnosed with head and neck paraganglioma, this alteration was detected in 1 individual (Neumann HP et al. Cancer Res, 2009 Apr;69:3650-6). In a yeast-based functional study, this alteration demonstrated normal function (Panizza E et al. Hum Mol Genet, 2013 Feb;22:804-15). 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. |