Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001376975 | SCV001574187 | pathogenic | not provided | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 444 of the LRP5 protein (p.Arg444Cys). This variant is present in population databases (rs80358308, gnomAD 0.004%). This missense change has been observed in individuals with autosomal dominant and recessive familial exudative vitreoretinopathy (PMID: 15981244, 26244290, 31237656, 34860240; Invitae). ClinVar contains an entry for this variant (Variation ID: 6293). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on LRP5 protein function. Experimental studies have shown that this missense change affects LRP5 function (PMID: 17955262). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000006673 | SCV000026856 | pathogenic | Exudative vitreoretinopathy 4, digenic | 2005-08-01 | no assertion criteria provided | literature only |