ClinVar Miner

Submissions for variant NM_182476.3(COQ6):c.782C>T (p.Pro261Leu)

gnomAD frequency: 0.00011  dbSNP: rs371260604
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000995743 SCV001150071 pathogenic Familial steroid-resistant nephrotic syndrome with sensorineural deafness 2019-06-07 criteria provided, single submitter clinical testing
GeneDx RCV001575270 SCV001802229 pathogenic not provided 2023-08-26 criteria provided, single submitter clinical testing Published functional studies involving transfection of P261L into COQ6 deficient yeast failed to rescue growth and mitochondrial complex II and III activity (Gigante et al., 2017); Not observed at a 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: 31937884, 30232548, 28044327, 28117207, 30584653, 35483523, 36245711)
3billion RCV000995743 SCV002573297 likely pathogenic Familial steroid-resistant nephrotic syndrome with sensorineural deafness 2022-09-01 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.007%). While this variant results in missense change, protein truncation variants are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (3Cnet: 0.96). It has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000807582). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 28117207). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
Invitae RCV001575270 SCV003442735 pathogenic not provided 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 261 of the COQ6 protein (p.Pro261Leu). This variant is present in population databases (rs371260604, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of coenzyme Q10 deficiency (PMID: 28044327, 28117207, 30584653, 31937884). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 807582). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000995743 SCV001468322 pathogenic Familial steroid-resistant nephrotic syndrome with sensorineural deafness 2021-01-04 no assertion criteria provided literature only

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