Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002536930 | SCV000930756 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2020-02-28 | 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SDHD-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with phenylalanine at codon 59 of the SDHD protein (p.Ser59Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. |
| Ambry Genetics | RCV001013090 | SCV001173630 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-15 | criteria provided, single submitter | clinical testing | The p.S59F variant (also known as c.176C>T), located in coding exon 3 of the SDHD gene, results from a C to T substitution at nucleotide position 176. The serine at codon 59 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is well 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. |