Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000210650 | SCV000262867 | likely pathogenic | Inborn genetic diseases | 2014-02-05 | criteria provided, single submitter | clinical testing | |
| Wellcome Centre for Mitochondrial Research, |
RCV000852404 | SCV000995087 | likely pathogenic | Mitochondrial disease | 2019-09-18 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001853374 | SCV002299548 | pathogenic | not provided | 2022-08-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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) performed at Invitae indicates that this missense variant is expected to disrupt COQ8A protein function. ClinVar contains an entry for this variant (Variation ID: 225002). This missense change has been observed in individuals with clinical features of coenzyme Q10 deficiency (PMID: 25131622, 32337771, 32685350; Invitae). It has also been observed to segregate with disease in related individuals. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 339 of the COQ8A protein (p.Ala339Thr). |
| 3billion | RCV003152697 | SCV003841305 | likely pathogenic | Autosomal recessive ataxia due to ubiquinone deficiency | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.75; 3Cnet: 0.94). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000225002). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 32685350). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |