Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000811684 | SCV000951963 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 | 2018-09-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 78 of the SDHD protein (p.Gly78Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHD-related disease. 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 C15"). 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 | RCV004028737 | SCV005020197 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-03-04 | criteria provided, single submitter | clinical testing | The p.G78R variant (also known as c.232G>C), located in coding exon 3 of the SDHD gene, results from a G to C substitution at nucleotide position 232. The glycine at codon 78 is replaced by arginine, an amino acid with dissimilar properties. This variant has been observed in at least one individual with a personal and/or family history that is consistent with SDHD-related paraganglioma-pheochromocytoma syndrome (Ambry internal data). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |