Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570801 | SCV000675031 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-06-29 | criteria provided, single submitter | clinical testing | The p.E154G variant (also known as c.461A>G), located in coding exon 5 of the SDHA gene, results from an A to G substitution at nucleotide position 461. The glutamic acid at codon 154 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
| Invitae | RCV000691114 | SCV000818857 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2021-04-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with glycine at codon 154 of the SDHA protein (p.Glu154Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with SDHA-related disease. ClinVar contains an entry for this variant (Variation ID: 486403). This variant is present in population databases (rs777873911, ExAC 0.006%). |