ClinVar Miner

Submissions for variant NM_174878.3(CLRN1):c.127G>A (p.Gly43Arg)

gnomAD frequency: 0.00004  dbSNP: rs111033434
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000041430 SCV000065125 likely pathogenic Rare genetic deafness 2013-11-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001058723 SCV001223314 pathogenic not provided 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 43 of the CLRN1 protein (p.Gly43Arg). This variant is present in population databases (rs111033434, gnomAD 0.002%). This missense change has been observed in individual(s) with clinical features of Usher syndrome, inherited retinal dystrophy, and/or retinitis pigmentosa (PMID: 32037395; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 48142). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Gly43 amino acid residue in CLRN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001058723 SCV002546574 likely pathogenic not provided 2022-07-07 criteria provided, single submitter clinical testing Reported with a second variant (phase unknown) in a patient with retinal degeneration in published literature (Zampaglione et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32037395)

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.