Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000475448 | SCV000553872 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-11-23 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 644 of the SDHA protein (p.Val644Met). This variant is present in population databases (rs3211483, gnomAD 0.03%). This missense change has been observed in individual(s) with dilated cardiomyopathy (DCM) (PMID: 28750076). ClinVar contains an entry for this variant (Variation ID: 412359). 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. |
| Counsyl | RCV000662992 | SCV000785983 | uncertain significance | Paragangliomas 5 | 2018-01-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002251478 | SCV002522117 | uncertain significance | not provided | 2022-05-09 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in a patient with cardiomyopathy (Forleo 2017); This variant is associated with the following publications: (PMID: 28750076) |
| Ambry Genetics | RCV002411517 | SCV002721301 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-24 | criteria provided, single submitter | clinical testing | The p.V644M variant (also known as c.1930G>A), located in coding exon 15 of the SDHA gene, results from a G to A substitution at nucleotide position 1930. The valine at codon 644 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Myriad Genetics, |
RCV000662992 | SCV004018602 | uncertain significance | Paragangliomas 5 | 2023-04-21 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
| Prevention |
RCV004533204 | SCV004119055 | uncertain significance | SDHA-related disorder | 2023-06-12 | criteria provided, single submitter | clinical testing | The SDHA c.1930G>A variant is predicted to result in the amino acid substitution p.Val644Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.031% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-256470-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Baylor Genetics | RCV003476126 | SCV004200610 | uncertain significance | Dilated cardiomyopathy 1GG | 2024-01-28 | criteria provided, single submitter | clinical testing |