Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001854492 | SCV002237244 | pathogenic | PRPH2-Related Disorders | 2021-08-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change replaces cysteine with arginine at codon 213 of the PRPH2 protein (p.Cys213Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with autosomal dominant pattern dystrophy and/or autosomal recessive Leber congenital amaurosis (PMID: 9443872, 23847139). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 98691). 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. This variant disrupts the p.Cys213 amino acid residue in PRPH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11934323, 21071739, 28559085). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. |
Retina International | RCV000085002 | SCV000117138 | not provided | not provided | no assertion provided | not provided | ||
OMIM | RCV000149468 | SCV000196112 | pathogenic | Patterned macular dystrophy 1 | 2013-10-01 | no assertion criteria provided | literature only | |
OMIM | RCV000149469 | SCV000196113 | pathogenic | Leber congenital amaurosis 18 | 2013-10-01 | no assertion criteria provided | literature only | |
Leiden Open Variation Database | RCV000085002 | SCV001745096 | likely pathogenic | not provided | 2021-04-06 | no assertion criteria provided | curation | Curator: Global Variome, with Curator vacancy. Submitter to LOVD: Manon Peeters. |