ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.1213C>T (p.Arg405Trp) (rs139842473)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487188 SCV000564888 likely pathogenic not provided 2018-02-12 criteria provided, single submitter clinical testing The R405W variant in the CLN3 gene has been reported previously in association with autosomal recessive retinal degeneration when present in the homozygous state or when in trans with another disease-causing CLN3 variant (Wang et al., 2014; Weisschuch et al., 2016; Ku et al., 2017). These individuals only had visual problems and lacked any neurological features associated with juvenile neuronal ceroid lipofuscinosis (Wang et al., 2014; Weisschuch et al., 2016; Ku et al., 2017). The R405W variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The R405W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret R405W as a likely pathogenic variant.
Invitae RCV000559381 SCV000628924 pathogenic Neuronal ceroid lipofuscinosis 2020-01-02 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 405 of the CLN3 protein (p.Arg405Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs139842473, ExAC 0.006%). This variant has been observed to segregate with autosomal recessive retinitis pigmentosa in a family and is present in additional unrelated individuals affected with retinitis pigmentosa (PMID: 28041643, 24154662, 26766544, 28559085). ClinVar contains an entry for this variant (Variation ID: 418137). 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"). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075708 SCV001241336 pathogenic Retinal dystrophy 2019-04-24 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001253588 SCV001429386 uncertain significance Juvenile neuronal ceroid lipofuscinosis 2019-05-16 criteria provided, single submitter clinical testing This variant was identified as homozygous
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504756 SCV000599193 likely pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research
Human Genetics - Radboudumc,Radboudumc RCV000504756 SCV000804615 likely pathogenic Retinitis pigmentosa 2016-09-01 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.