Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000467274 | SCV000553871 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-12-08 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 160 of the SDHA protein (p.Phe160Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with mitochondrial complex Ii deficiency (PMID: 34645491). ClinVar contains an entry for this variant (Variation ID: 412358). 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 | RCV000662662 | SCV000785351 | uncertain significance | Paragangliomas 5 | 2017-07-20 | criteria provided, single submitter | clinical testing | |
| Rady Children's Institute for Genomic Medicine, |
RCV000853253 | SCV000996074 | likely pathogenic | Mitochondrial complex II deficiency, nuclear type 1 | 2017-09-21 | criteria provided, single submitter | clinical testing | This variant has not previously been reported in public databases, and is thus presumed to be rare. The p.Phe160 residue is highly conserved among eukaryotes and in silico models predict a damaging effect of the leucine substitution on protein function. The SDHA protein is missense variant intolerant according to data in the ExAC database. The p.Phe160Leu has not previously been described in ClinVar or functionally characterized. For these reasons the variant is classified as Likely Pathogenic. |
| Ambry Genetics | RCV002341056 | SCV002637812 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-22 | criteria provided, single submitter | clinical testing | The p.F160L variant (also known as c.480T>G), located in coding exon 5 of the SDHA gene, results from a T to G substitution at nucleotide position 480. The phenylalanine at codon 160 is replaced by leucine, an amino acid with highly similar properties. This alteration has been reported in conjunction with SDHA c.1795-1G>T in an infant with mitochondrial II complex deficiency (Owen MJ et al. JAMA Netw Open, 2023 Feb;6:e2254069). 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. |
| Myriad Genetics, |
RCV000662662 | SCV004018619 | 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. |
| Baylor Genetics | RCV003476125 | SCV004200617 | uncertain significance | Dilated cardiomyopathy 1GG | 2023-07-21 | criteria provided, single submitter | clinical testing |