ClinVar Miner

Submissions for variant NM_020247.5(COQ8A):c.1000C>T (p.Arg334Trp)

gnomAD frequency: 0.00005  dbSNP: rs373971613
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000502514 SCV000593041 likely pathogenic Autosomal recessive ataxia due to ubiquinone deficiency 2017-02-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001857069 SCV002312411 likely pathogenic not provided 2023-12-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 334 of the COQ8A protein (p.Arg334Trp). This variant is present in population databases (rs373971613, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of primary coenzyme Q10 deficiency and/or clinical features of primary coenzyme Q10 deficiency (PMID: 29915382). 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: 434088). 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 COQ8A protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV001857069 SCV005079332 uncertain significance not provided 2024-05-17 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: 29915382)

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