Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001056822 | SCV001221286 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2019-03-02 | criteria provided, single submitter | clinical testing | 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"). 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. This variant has not been reported in the literature in individuals with SDHC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 41 of the SDHC protein (p.Phe41Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. |
| Ambry Genetics | RCV003307883 | SCV004000440 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-15 | criteria provided, single submitter | clinical testing | The p.F41S variant (also known as c.122T>C), located in coding exon 3 of the SDHC gene, results from a T to C substitution at nucleotide position 122. The phenylalanine at codon 41 is replaced by serine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |