ClinVar Miner

Submissions for variant NM_006205.3(PDE6H):c.35C>G (p.Ser12Ter)

gnomAD frequency: 0.00012  dbSNP: rs200311463
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000779093 SCV000915582 likely pathogenic PDE6H-related disorder 2018-08-23 criteria provided, single submitter clinical testing The PDE6H c.35C>G (p.Ser12Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The p.Ser12Ter variant has been reported in two studies and is found in a homozygous state in five probands from three families including two sibling pairs (Kohl et al. 2012; Pedurupillay et al. 2016). Three of the probands are diagnosed with incomplete achromatopsia and two with cone dystrophy. The unaffected parents of the siblings were confirmed heterozygotes for the p.Ser12Ter variant. The p.Ser12Ter variant was absent from 180 control subjects and is reported at a frequency of 0.000166 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the potential impact of stop-gained variants and evidence from the literature, the p.Ser12Ter variant is classified as likely pathogenic for PDE6H-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
CeGaT Center for Human Genetics Tuebingen RCV001092385 SCV001248872 pathogenic not provided 2020-11-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000055928 SCV001369732 uncertain significance Retinal cone dystrophy 3A 2019-12-04 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to conclusively support its pathogenic nature. Thus this variant is classified as Uncertain significance - favor pathogenic. The following ACMG criteria were applied in classifying this variant: PP3,PP5.
Invitae RCV001092385 SCV002227721 pathogenic not provided 2024-01-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser12*) in the PDE6H gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PDE6H are known to be pathogenic (PMID: 22901948, 27472364). This variant is present in population databases (rs200311463, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with achromatopsia (PMID: 22901948, 27472364). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 37245). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, Heidelberg University RCV000055928 SCV002556342 likely pathogenic Retinal cone dystrophy 3A 2022-05-23 criteria provided, single submitter clinical testing
OMIM RCV000030807 SCV000053478 pathogenic Achromatopsia 6 2012-09-07 no assertion criteria provided literature only
GeneReviews RCV000055928 SCV000086940 not provided Retinal cone dystrophy 3A no assertion provided literature only
Department of Medical Genetics, Oslo University Hospital RCV000055928 SCV000256082 pathogenic Retinal cone dystrophy 3A 2015-10-27 no assertion criteria provided research
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001092385 SCV001957650 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001092385 SCV001971195 pathogenic not provided no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.