Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000214185 | SCV000274554 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-25 | criteria provided, single submitter | clinical testing | The p.R379C variant (also known as c.1135C>T), located in coding exon 9 of the SDHA gene, results from a C to T substitution at nucleotide position 1135. The arginine at codon 379 is replaced by cysteine, an amino acid with highly dissimilar 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. |
Invitae | RCV000459361 | SCV000553873 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 379 of the SDHA protein (p.Arg379Cys). This variant is present in population databases (rs749309213, gnomAD 0.007%). 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: 230873). 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
Center for Pediatric Genomic Medicine, |
RCV000514432 | SCV000610367 | uncertain significance | not provided | 2017-05-11 | criteria provided, single submitter | clinical testing |