ClinVar Miner

Submissions for variant NM_178857.6(RP1L1):c.133C>T (p.Arg45Trp) (rs267607017)

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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 RCV000726920 SCV000704172 likely pathogenic not provided 2016-12-21 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000002277 SCV000916218 uncertain significance Occult macular dystrophy 2017-08-22 criteria provided, single submitter clinical testing The RP1L1 c.133C>T (p.Arg45Trp) missense variant has been reported in at least six studies and is found in a heterozygous state in a total of 35 individuals with occult macular dystrophy, including 15 unrelated individuals. The variant is also found in 13 unaffected family members (Akahori et al. 2010; Okuno et al. 2013; Hayashi et al. 2012; Davidson et al. 2013; Piermarocchi et al. 2016; Fujinami al. 2016). Due to the presence of both affected and unaffected family members carrying the p.Arg45Trp variant in a heterozygous state, Akahori et al. (2010) and Davidson et al. (2013) suggest that the variant may exhibit reduced penetrance or later age of onset in asymptomatic carriers. The p.Arg45Trp variant was absent from 976 controls but is reported at a frequency of 0.000025 in the total population of the Genome Aggregation Database. Based on the evidence, the p.Arg45Trp variant is classified a variant of unknown significance but suspicious for pathogenicity for occult macular dystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Blueprint Genetics RCV001074376 SCV001239954 pathogenic Retinal dystrophy 2019-07-30 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000726920 SCV001245752 pathogenic not provided 2021-01-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001197672 SCV001368451 pathogenic Retinitis pigmentosa 88 2019-12-03 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PP1-S,PP3.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000726920 SCV001447606 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Invitae RCV000726920 SCV001585398 pathogenic not provided 2020-10-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 45 of the RP1L1 protein (p.Arg45Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs267607017, ExAC 0.01%). This variant has been observed in individual(s) with occult macular dystrophy (PMID: 20826268, 30025130). It has also been observed to segregate with disease in related individuals. This variant is also known as c.362C>T. ClinVar contains an entry for this variant (Variation ID: 2193). 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: Benign; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000726920 SCV001770569 likely pathogenic not provided 2021-09-07 criteria provided, single submitter clinical testing Reduced penetrance has been reported for the R45W variant (Zobor et al., 2018); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32360662, 32458067, 32531858, 32940107, 32176261, 22504327, 23281133, 23745001, 27623337, 31028767, 31193770, 28195981, 27579568, 30025130, 28890726, 29555955, 22466457, 20826268, 26782618, 23619761, 25908487)
OMIM RCV000002277 SCV000022435 risk factor Occult macular dystrophy 2013-03-01 no assertion criteria provided literature only
Clinical Genetics,Academic Medical Center RCV000726920 SCV001922196 pathogenic not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000726920 SCV001955747 likely pathogenic not provided no assertion criteria provided clinical testing

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