Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000694799 | SCV000823260 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 159 of the SDHC protein (p.Thr159Ile). 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: 573194). 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. |
| Ambry Genetics | RCV002334309 | SCV002638659 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-04 | criteria provided, single submitter | clinical testing | The p.T159I variant (also known as c.476C>T), located in coding exon 6 of the SDHC gene, results from a C to T substitution at nucleotide position 476. The threonine at codon 159 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is 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. |