Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001380061 | SCV001577996 | pathogenic | not provided | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 382 of the LRP5 protein (p.Pro382Leu). This variant is present in population databases (rs397514664, gnomAD 0.0009%). This missense change has been observed in individuals with autosomal dominant familial exudative vitreoretinopathy and autosomal recessive osteoporosis-pseudoglioma syndrome (PMID: 20034086, 29131652, 30452590). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 40288). 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. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000033258 | SCV000057141 | pathogenic | Osteoporosis with pseudoglioma | 2010-01-01 | no assertion criteria provided | literature only |