Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Fulgent Genetics, |
RCV005003492 | SCV002810926 | likely pathogenic | 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 | 2024-05-30 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002516009 | SCV003440342 | likely pathogenic | not provided | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1188 of the LRP5 protein (p.Arg1188Trp). This variant is present in population databases (rs141178995, gnomAD 0.005%). This missense change has been observed in individual(s) with autosomal dominant polycystic liver disease (PMID: 24706814). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 162391). 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. Experimental studies have shown that this missense change affects LRP5 function (PMID: 24706814). 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. |
| Laboratory of Gastroenterology and Hepatology, |
RCV000149786 | SCV000196580 | not provided | Polycystic liver disease 1 | no assertion provided | not provided | ||
| OMIM | RCV000584769 | SCV000692481 | pathogenic | Polycystic liver disease 4 with or without kidney cysts | 2014-04-08 | no assertion criteria provided | literature only |