Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000698751 | SCV000827435 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2018-06-23 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SDHA-related disease. This sequence change replaces glutamic acid with alanine at codon 473 of the SDHA protein (p.Glu473Ala). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and alanine. |
| Ambry Genetics | RCV003352990 | SCV004071258 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-30 | criteria provided, single submitter | clinical testing | The p.E473A variant (also known as c.1418A>C), located in coding exon 10 of the SDHA gene, results from an A to C substitution at nucleotide position 1418. The glutamic acid at codon 473 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |