Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000526392 | SCV000651441 | pathogenic | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 152 of the SDHA protein (p.Glu152Lys). This variant is present in population databases (rs778737664, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of autosomal recessive mitochondrial complex II deficiency (PMID: 33960148; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 472390). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV001022683 | SCV001184444 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-17 | criteria provided, single submitter | clinical testing | The p.E152K variant (also known as c.454G>A), located in coding exon 4 of the SDHA gene, results from a G to A substitution at nucleotide position 454. The glutamic acid at codon 152 is replaced by lysine, an amino acid with similar properties. This alteration has been identified in trans with a pathogenic SDHA mutation in a patient with a respiratory chain disorder (Sturrock BRH et al. Mol Genet Genomic Med, 2021 Jun;9:e1692). 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 |
RCV003231529 | SCV003929608 | uncertain significance | not provided | 2022-11-30 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33960148) |
| Baylor Genetics | RCV003476313 | SCV004200562 | uncertain significance | Dilated cardiomyopathy 1GG | 2023-09-25 | criteria provided, single submitter | clinical testing | |
| Undiagnosed Diseases Network, |
RCV002509437 | SCV002818550 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1 | 2022-08-04 | no assertion criteria provided | clinical testing |