Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute Of Human Genetics Munich, |
RCV000578266 | SCV000680180 | likely pathogenic | Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome | 2017-12-11 | criteria provided, single submitter | clinical testing | |
Genomic Research Center, |
RCV000578266 | SCV000746530 | likely pathogenic | Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome | 2017-12-03 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000659124 | SCV000780938 | uncertain significance | not provided | 2018-03-01 | criteria provided, single submitter | clinical testing | |
Centogene AG - |
RCV000578266 | SCV001426599 | pathogenic | Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome | criteria provided, single submitter | clinical testing | ||
Institute of Medical Genetics and Applied Genomics, |
RCV000659124 | SCV001447366 | likely pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Kariminejad - |
RCV001814189 | SCV001755392 | likely pathogenic | Abnormality of the nervous system | 2021-07-10 | criteria provided, single submitter | clinical testing | |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000578266 | SCV002073117 | likely pathogenic | Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome | criteria provided, single submitter | clinical testing | The missense variant p.F146C in COQ4 (NM_016035.5) has been previously reported (Bertoli-Avella AM et al). The variant has been submitted to ClinVar as Pathogenic/Likely pathogenic and Uncertain Significance. The p.F146C variant is observed in 1/2,25,000 (0.0004%) alleles from individuals of all background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.F146C missense variant is predicted to be damaging by both SIFT and PolyPhen2. The phenylalanine residue at codon 146 of COQ4 is conserved in all mammalian species. The nucleotide c.437 in COQ4 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic. | |
MGZ Medical Genetics Center | RCV000578266 | SCV002580760 | likely pathogenic | Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome | 2022-01-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000578266 | SCV003304258 | uncertain significance | Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome | 2022-01-18 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 488487). This missense change has been observed in individuals with coenzyme Q10 deficiency (PMID: 32860008, 33215859). This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 146 of the COQ4 protein (p.Phe146Cys). |
Myelin Disorders Clinic- |
RCV000578266 | SCV001245480 | uncertain significance | Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome | no assertion criteria provided | clinical testing |