ClinVar Miner

Submissions for variant NM_020247.5(COQ8A):c.911C>T (p.Ala304Val) (rs748118737)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000427376 SCV000521310 likely pathogenic not provided 2016-10-19 criteria provided, single submitter clinical testing The A304V variant in the ADCK3 gene has been reported previously in the homozygous state in anindividual reported to have adult onset cerebellar ataxia, tremor, myoclonus and muscle weakness(Horvath et al., 2012). The A304V variant was not observed in approximately 6500 individuals ofEuropean and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is nota common benign variant in these populations. The A304V variant is a conservative amino acidsubstitution, which is not likely to impact secondary protein structure as these residues share similarproperties. However, this substitution occurs at a position that is conserved across species and in silicoanalysis predicts this variant is probably damaging to the protein structure/function. The A304Vvariant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benignvariant cannot be excluded.
Illumina Clinical Services Laboratory,Illumina RCV000778971 SCV000915399 uncertain significance ADCK3-Related Disorders 2018-08-10 criteria provided, single submitter clinical testing The ADCK3 c.911C>T (p.Ala304Val) missense variant has been reported in two studies in which it is identified in a homozygous state in two unrelated individuals with cerebellar ataxia (Horvath et al. 2012; Mallaret et al. 2016). It was also described in an individual with coenzyme Q deficiency (Hughes et al. 2017). The p.Ala304Val variant was absent from 100 controls but is reported at a frequency of 0.000079 in the European (non-Finnish) population of the Genome Aggregation Database. Another missense variant at this position, p.Ala304Thr, has also been reported in affected individuals (Horvath et al. 2012). Multiple in silico tools predict a deleterious effect of the variant, but functional studies have not been conducted. The evidence for this variant is limited. Therefore, the p.Ala304Val variant is classified as of uncertain significance but suspicious for pathogenicity for ADCK3-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000427376 SCV001335227 uncertain significance not provided 2020-03-01 criteria provided, single submitter clinical testing

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