Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000546880 | SCV000651345 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2020-11-19 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with threonine at codon 347 of the SDHA protein (p.Met347Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an SDHA-related disease. |
| Ambry Genetics | RCV002395442 | SCV002696812 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-19 | criteria provided, single submitter | clinical testing | The p.M347T variant (also known as c.1040T>C), located in coding exon 8 of the SDHA gene, results from a T to C substitution at nucleotide position 1040. The methionine at codon 347 is replaced by threonine, 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. |