Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001237344 | SCV001410101 | likely pathogenic | not provided | 2024-02-23 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 79 of the LRP5 protein (p.Trp79Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal recessive LRP5-related conditions (PMID: 25384351, 28192794). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 963332). 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 with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Fulgent Genetics, |
RCV005050303 | SCV005684289 | uncertain significance | Bone mineral density quantitative trait locus 1; Exudative vitreoretinopathy 4; Worth disease; Autosomal dominant osteopetrosis 1; Osteoporosis with pseudoglioma; Polycystic liver disease 4 with or without kidney cysts | 2024-05-14 | criteria provided, single submitter | clinical testing |