Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics Munich, |
RCV000995743 | SCV001150071 | pathogenic | Familial steroid-resistant nephrotic syndrome with sensorineural deafness | 2019-06-07 | criteria provided, single submitter | clinical testing | |
Gene |
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 |