ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.421T>C (p.Tyr141His)

dbSNP: rs61755780
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002513911 SCV003439414 pathogenic PRPH2-related disorder 2023-11-13 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 141 of the PRPH2 protein (p.Tyr141His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of PRPH2-related conditions (PMID: 11139263, 17653047, 34327195; Invitae). ClinVar contains an entry for this variant (Variation ID: 98665). 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 expected to disrupt PRPH2 protein function with a positive predictive value of 95%. This variant disrupts the p.Tyr141 amino acid residue in PRPH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16113362, 16799052, 25001182, 25082885, 25097241). 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.
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV004815030 SCV005070900 likely pathogenic Retinal dystrophy 2021-01-01 criteria provided, single submitter clinical testing
Retina International RCV000084968 SCV000117104 not provided not provided no assertion provided not provided
Leiden Open Variation Database RCV000084968 SCV001745047 pathogenic not provided 2021-04-06 no assertion criteria provided curation Curator: Global Variome, with Curator vacancy. Submitter to LOVD: Manon Peeters.

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.