Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000806830 | SCV000946849 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-09-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 367 of the SDHA protein (p.Gln367Glu). 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 not expected to disrupt SDHA protein function. ClinVar contains an entry for this variant (Variation ID: 651462). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. This variant is present in population databases (rs780941330, gnomAD 0.01%). |
Ambry Genetics | RCV003166259 | SCV003904063 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-02 | criteria provided, single submitter | clinical testing | The p.Q367E variant (also known as c.1099C>G), located in coding exon 9 of the SDHA gene, results from a C to G substitution at nucleotide position 1099. The glutamine at codon 367 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
Genome |
RCV000806830 | SCV001749367 | not provided | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | no assertion provided | phenotyping only | Variant interpreted as Uncertain significance and reported on 06-11-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |