ClinVar Miner

Submissions for variant NM_000440.3(PDE6A):c.304C>A (p.Arg102Ser) (rs141252097)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000173136 SCV000224224 uncertain significance not provided 2015-03-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000407624 SCV000454707 likely pathogenic Retinitis pigmentosa 2016-09-20 criteria provided, single submitter clinical testing The PDE6A c.304C>A (p.Arg102Ser) missense variant has been reported in several studies. The variant was first reported by Dryja et al. (1999), who identified the variant in a compound heterozygous state in a sibling pair affected with autosomal recessive retinitis pigmentosa (arRP) and in a heterozygous state in the unaffected father and an unaffected sibling. Maria et al. (2015) later reported the variant in a homozygous state in a total of five individuals, including two sibling pairs, from a large consanguineous family affected with arRP. The variant was also identified in a heterozygous state in nine unaffected family members. The p.Arg102Ser variant has been further reported in 14 additional individuals, including in a heterozygous state with no second identified variant in a sibling pair affected with arRP, in 11 individuals with arRP where zygosity information is not provided, and in a heterozygous state in an individual with an unidentified retinal disorder (Avila-Fernandez et al. 2010; Booij et al. 2011; Abu-Safieh et al. 2013; van Huet et al. 2015). The p.Arg102Ser variant was absent from 70 controls (Dryja et al. 1999) and is reported at a frequency of 0.00018 in the South Asian population of the Exome Aggregation Consortium. The Arg102 residue is located in the GMP binding domain in exon 1 and is conserved (Dryja et al. 1999). Based on the collective evidence, the p.Arg102Ser variant is classified as likely pathogenic for autosomal recessive retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000173136 SCV001210315 pathogenic not provided 2020-09-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 102 of the PDE6A protein (p.Arg102Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is present in population databases (rs141252097, ExAC 0.02%). This variant has been observed in individuals affected with autosomal recessive retinitis pigmentosa (arRP) and segregated with arRP in several families (PMID: 10393062, 27917291, 25775262, 26868535). ClinVar contains an entry for this variant (Variation ID: 193099). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001073620 SCV001239171 pathogenic Retinal dystrophy 2019-07-19 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000173136 SCV001245889 pathogenic not provided 2017-03-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000173136 SCV001447879 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001376501 SCV001573674 likely pathogenic Retinitis pigmentosa 43 2021-04-08 criteria provided, single submitter research The PDE6A c.304C>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PS1, PM2, PP1. Based on this evidence we have classified this variant as Likely Pathogenic.
Sharon lab,Hadassah-Hebrew University Medical Center RCV000407624 SCV001161182 likely pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research
Faculty of Health Sciences,Beirut Arab University RCV001257852 SCV001434619 pathogenic Autosomal recessive retinitis pigmentosa 2012-10-26 no assertion criteria provided literature only
Clinical Genetics,Academic Medical Center RCV000173136 SCV001924675 likely pathogenic not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000173136 SCV001957692 likely pathogenic not provided no assertion criteria provided clinical testing

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