Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000414333 | SCV000490604 | likely pathogenic | not provided | 2022-08-23 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect: affects Wnt1 signaling (Bhat 2007); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (Lek 2006).; This variant is associated with the following publications: (PMID: 28420620, 11719191, 15143163, 16252235, 31827910, 30452590, 34426522, 16390319, 35106624, 21528003, 27535533, 17276019) |
| Invitae | RCV000414333 | SCV001531715 | pathogenic | not provided | 2022-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 494 of the LRP5 protein (p.Arg494Gln). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg494 amino acid residue in LRP5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30452590; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects LRP5 function (PMID: 21528003, 28420620). 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 LRP5 protein function. ClinVar contains an entry for this variant (Variation ID: 6274). This missense change has been observed in individuals with autosomal dominant familial exudative vitreoretinopathy and autosomal recessive osteoporosis-pseudoglioma syndrome (PMID: 11719191, 28420620, 35106624). |
| Mendelics | RCV002247255 | SCV002517583 | pathogenic | Exudative vitreoretinopathy 1 | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002482834 | SCV002778094 | likely pathogenic | Bone mineral density quantitative trait locus 1; Exudative vitreoretinopathy 4; Exudative vitreoretinopathy 1; Worth disease; Autosomal dominant osteopetrosis 1; Osteoporosis with pseudoglioma; Osteoporosis; Polycystic liver disease 4 with or without kidney cysts | 2022-03-07 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000006652 | SCV000026835 | pathogenic | Osteoporosis with pseudoglioma | 2001-11-16 | no assertion criteria provided | literature only |