Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000460826 | SCV000553887 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2024-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 591 of the SDHA protein (p.Ala591Thr). This variant is present in population databases (rs1042170, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of SDHA-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 412370). 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. |
| Ambry Genetics | RCV001013059 | SCV001173596 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-27 | criteria provided, single submitter | clinical testing | The p.A591T variant (also known as c.1771G>A), located in coding exon 13 of the SDHA gene, results from a G to A substitution at nucleotide position 1771. The alanine at codon 591 is replaced by threonine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with a paraganglioma and/or pheochromocytoma however they were also identified to carry an SDHD alteration (Meijs AC et al. J Endocrinol Invest, 2021 Oct;44:2253-2259). 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. |
| Gene |
RCV003441889 | SCV004169268 | uncertain significance | not provided | 2023-04-28 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in an individual with multiple paraganglioma who also carried a splice variant in the SDHD gene (PMID: 33715142); This variant is associated with the following publications: (PMID: 33715142) |
| Baylor Genetics | RCV003476130 | SCV004200558 | uncertain significance | Dilated cardiomyopathy 1GG | 2023-09-26 | criteria provided, single submitter | clinical testing |