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

dbSNP: rs141252097

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000173136	SCV000224224	uncertain significance	not provided	2015-03-05	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, 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	2024-01-31	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 102 of the PDE6A protein (p.Arg102Ser). This variant is present in population databases (rs141252097, gnomAD 0.03%). This missense change has been observed in individuals with autosomal recessive retinitis pigmentosa (arRP) (PMID: 10393062, 25775262, 26868535, 27917291). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 193099). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PDE6A protein function with a negative predictive value of 80%. 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 Center for Human Genetics 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.
MGZ Medical Genetics Center	RCV001376501	SCV002579894	likely pathogenic	Retinitis pigmentosa 43	2022-05-23	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001376501	SCV003808768	likely pathogenic	Retinitis pigmentosa 43	2022-02-24	criteria provided, single submitter	clinical testing
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
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000173136	SCV001957692	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000173136	SCV001971929	likely pathogenic	not provided		no assertion criteria provided	clinical testing
OMIM	RCV001376501	SCV003844048	pathogenic	Retinitis pigmentosa 43	2023-03-23	no assertion criteria provided	literature only