Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001306997 | SCV001496390 | uncertain significance | not provided | 2024-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1227 of the LRP5 protein (p.Ile1227Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with LRP5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1009494). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt LRP5 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Fulgent Genetics, |
RCV002476411 | SCV002790745 | uncertain significance | 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 | 2022-01-18 | criteria provided, single submitter | clinical testing | |
| Johns Hopkins Genomics, |
RCV003320375 | SCV004024526 | uncertain significance | Polycystic liver disease 4 with or without kidney cysts | 2023-05-25 | criteria provided, single submitter | clinical testing | This LRP5 missense variant (rs949211640) is rare (<0.1%) in a large population dataset (gnomAD v2.1.1: 3/251420 total alleles; 0.001%; no homozygotes). It has been reported in ClinVar (Variation ID 1009494), but has not been reported in the literature, to our knowledge. Of two bioinformatics tools queried, one predicts that the substitution would be damaging, while the other predicts that it would be tolerated. The isoleucine residue at this position is evolutionarily conserved across most of the species assessed. At this time, there is limited evidence for the association of LRP5 with polycystic liver disease 4 with or without kidney cysts. We consider the clinical significance of c.3679A>G in LRP5 to be uncertain. |