Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001853076 | SCV002176239 | uncertain significance | not provided | 2022-11-15 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this missense change affects COQ2 function (PMID: 23758206). 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 not expected to disrupt COQ2 protein function. ClinVar contains an entry for this variant (Variation ID: 60536). This missense change has been observed in individual(s) with multiple system atrophy (PMID: 23758206). This variant is present in population databases (rs778094136, gnomAD 0.07%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 128 of the COQ2 protein (p.Met128Val). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271394 | SCV002556118 | likely pathogenic | Coenzyme Q10 deficiency, primary, 1 | 2022-06-23 | criteria provided, single submitter | clinical testing | Variant summary: COQ2 c.382A>G (p.Met128Val) results in a conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 212966 control chromosomes (gnomAD). c.382A>G has been reported in the literature in at least two homozygous siblings affected with Multiple System Atrophy (Multiple-System Atrophy Research Collaboration_2013). These individuals were also homozygous for p.Val343Ala, which is considered a benign polymorphism (ClinVar:214217). These data indicate that the variant is likely to be associated with disease. Several publications have examined the functional impact of the variant: the variant could not rescue growth in a COQ2-null yeast strain (Multiple-System Atrophy Research Collaboration_2013); COQ2-null yeast expressing the the variant had decreased expression of other Coenzyme Q genes (COQ6, Desbats_2016); COQ2-null yeast had reduced oxygen consumption rate compared to wild-type (Yasuda_2019). Two ClinVar submitters have assessed the variant since 2014: one classified the variant as VUS, and one as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV002490627 | SCV002783673 | uncertain significance | Coenzyme Q10 deficiency, primary, 1; Multiple system atrophy 1, susceptibility to | 2022-02-04 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002515736 | SCV003563991 | uncertain significance | Inborn genetic diseases | 2021-12-23 | criteria provided, single submitter | clinical testing | The c.382A>G (p.M128V) alteration is located in exon 1 (coding exon 1) of the COQ2 gene. This alteration results from a A to G substitution at nucleotide position 382, causing the methionine (M) at amino acid position 128 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Breakthrough Genomics, |
RCV001853076 | SCV005190155 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
| OMIM | RCV000054428 | SCV000082905 | risk factor | Multiple system atrophy | 2014-07-03 | no assertion criteria provided | literature only | |
| Gene |
RCV000416397 | SCV000494119 | not provided | Coenzyme Q10 deficiency | no assertion provided | literature only |