Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
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, |
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 | |
Gene |
RCV000000459 | SCV000494142 | not provided | Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome | no assertion provided | literature only |