Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000458782 | SCV000546029 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2024-04-29 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 99 of the SDHC protein (p.Tyr99Cys). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 407052). 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. |
| All of Us Research Program, |
RCV004000758 | SCV004834456 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2024-01-11 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004659041 | SCV005161241 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-04 | criteria provided, single submitter | clinical testing | The p.Y99C variant (also known as c.296A>G), located in coding exon 5 of the SDHC gene, results from an A to G substitution at nucleotide position 296. The tyrosine at codon 99 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |