Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000543362 | SCV000651408 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 592 of the SDHA protein (p.His592Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with paraganglioma-pheochromocytoma syndromes (PMID: 30877234). ClinVar contains an entry for this variant (Variation ID: 472357). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 | RCV002404529 | SCV002713930 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-20 | criteria provided, single submitter | clinical testing | The p.H592R variant (also known as c.1775A>G), located in coding exon 13 of the SDHA gene, results from an A to G substitution at nucleotide position 1775. The histidine at codon 592 is replaced by arginine, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with a paraganglioma and/or pheochromocytoma (Ben Aim L et al. J Med Genet, 2019 08;56:513-520). 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. |