Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003556102 | SCV004294913 | pathogenic | not provided | 2023-07-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 40287). This missense change has been observed in individual(s) with clinical features of familial exudative vitreoretinopathy (PMID: 20034086, 26355662, 35876299; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 552 of the LRP5 protein (p.Thr552Met). |
| OMIM | RCV000033257 | SCV000057140 | pathogenic | Osteoporosis with pseudoglioma | 2010-01-01 | no assertion criteria provided | literature only |