Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001935549 | SCV002194537 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2021-06-20 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with tyrosine at codon 596 of the SDHA protein (p.Asp596Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is present in population databases (rs371304688, ExAC 0.002%). This variant has not been reported in the literature in individuals with SDHA-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SDHA protein function. 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 | RCV002397912 | SCV002714401 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-10 | criteria provided, single submitter | clinical testing | The p.D596Y variant (also known as c.1786G>T), located in coding exon 13 of the SDHA gene, results from a G to T substitution at nucleotide position 1786. The aspartic acid at codon 596 is replaced by tyrosine, an amino acid with highly dissimilar 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. |