Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000696212 | SCV000824764 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 477 of the SDHA protein (p.Pro477Leu). This variant is present in population databases (rs146990772, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 574308). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
Ce |
RCV000998346 | SCV001154357 | uncertain significance | not provided | 2017-03-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002388266 | SCV002698503 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-23 | criteria provided, single submitter | clinical testing | The p.P477L variant (also known as c.1430C>T), located in coding exon 10 of the SDHA gene, results from a C to T substitution at nucleotide position 1430. The proline at codon 477 is replaced by leucine, 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000998346 | SCV004220272 | uncertain significance | not provided | 2023-09-06 | criteria provided, single submitter | clinical testing | This variant has not been reported in individuals affected with SDHA related disease in the published literature. The frequency of this variant in the general population, 0.000023 (3/128868 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant. |