Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000794345 | SCV000933745 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2018-07-10 | criteria provided, single submitter | clinical testing | 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 leucine with methionine at codon 562 of the SDHA protein (p.Leu562Met). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and methionine. 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. |
| Ambry Genetics | RCV002397577 | SCV002712535 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-21 | criteria provided, single submitter | clinical testing | The p.L562M variant (also known as c.1684C>A), located in coding exon 13 of the SDHA gene, results from a C to A substitution at nucleotide position 1684. The leucine at codon 562 is replaced by methionine, an amino acid with highly 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. |