ClinVar Miner

Submissions for variant NM_020312.4(COQ9):c.730C>T (p.Arg244Ter)

gnomAD frequency: 0.00002  dbSNP: rs267606751
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000000459 SCV000917263 pathogenic Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome 2020-05-13 criteria provided, single submitter clinical testing Variant summary: COQ9 c.730C>T (p.Arg244X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.2e-05 in 251792 control chromosomes. c.730C>T has been reported in the literature in at-least one individual affected with Autosomal-Recessive Neonatal-Onset Primary Coenzyme Q10 Deficiency (Coenzyme Q10 Deficiency, Primary, 5, Duncan_2009). These data indicate that the variant is likely to be associated with disease. Several publications report experimental evidence and mouse models evaluating an impact on protein function (example, Duncan_2009, Lopez_2010, Garcia-Corzo_2013, Luna-Sanchez_2015, Quinzii_2010). The most pronounced variant effect resulted in ~10% of the normal coenzyme Q10 biosynthesis rate (Duncan_2009), and the generation of a homozygous mouse model with the orthologous variant R239X showed a severe CoQ10 deficiency (Garcia-Corzo_2013, Hidalgo-Gutierrez_2019). One reputed database (GeneReviews) has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital RCV000000459 SCV001984510 pathogenic Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome 2020-03-19 criteria provided, single submitter clinical testing
Invitae RCV003546449 SCV004266245 pathogenic not provided 2023-08-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg244*) in the COQ9 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COQ9 are known to be pathogenic (PMID: 19375058, 26081641). This variant is present in population databases (rs267606751, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with coenzyme Q10 deficiency (PMID: 19375058). ClinVar contains an entry for this variant (Variation ID: 431). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000459 SCV000020608 pathogenic Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome 2010-10-01 no assertion criteria provided literature only
GeneReviews RCV000000459 SCV000494142 not provided Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome no assertion provided literature only

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