Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000817037 | SCV000957573 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2019-12-07 | 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SDHA-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 643 of the SDHA protein (p.Pro643Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. |
| Ambry Genetics | RCV002406866 | SCV002719849 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-12 | criteria provided, single submitter | clinical testing | The p.P643S variant (also known as c.1927C>T), located in coding exon 15 of the SDHA gene, results from a C to T substitution at nucleotide position 1927. The proline at codon 643 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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. |