Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000816860 | SCV000957387 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2021-12-27 | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 659802). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 122 of the SDHA protein (p.His122Arg). |
Fulgent Genetics, |
RCV002495158 | SCV002798333 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Dilated cardiomyopathy 1GG; Paragangliomas 5; Neurodegeneration with ataxia and late-onset optic atrophy | 2022-01-18 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003307530 | SCV003996992 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-20 | criteria provided, single submitter | clinical testing | The p.H122R variant (also known as c.365A>G), located in coding exon 4 of the SDHA gene, results from an A to G substitution at nucleotide position 365. The histidine at codon 122 is replaced by arginine, an amino acid with highly 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. |