Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000801678 | SCV000941467 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2021-03-23 | criteria provided, single submitter | clinical testing | 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. 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. This variant has not been reported in the literature in individuals with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 647219). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with asparagine at codon 592 of the SDHA protein (p.His592Asn). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and asparagine. |
Ambry Genetics | RCV002397618 | SCV002711872 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-08 | criteria provided, single submitter | clinical testing | The p.H592N variant (also known as c.1774C>A), located in coding exon 13 of the SDHA gene, results from a C to A substitution at nucleotide position 1774. The histidine at codon 592 is replaced by asparagine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |