ClinVar Miner

Submissions for variant NM_016035.5(COQ4):c.437T>G (p.Phe146Cys)

dbSNP: rs1163170578
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Total submissions: 10
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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 RCV000578266 SCV000680180 likely pathogenic Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome 2017-12-11 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000578266 SCV000746530 likely pathogenic Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome 2017-12-03 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000659124 SCV000780938 uncertain significance not provided 2018-03-01 criteria provided, single submitter clinical testing
Centogene AG - the Rare Disease Company RCV000578266 SCV001426599 pathogenic Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000659124 SCV001447366 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center RCV001814189 SCV001755392 likely pathogenic Abnormality of the nervous system 2021-07-10 criteria provided, single submitter clinical testing
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine 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-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence, RCV000578266 SCV001245480 uncertain significance Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome no assertion criteria provided clinical testing

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