Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001213170 | SCV001384788 | uncertain significance | not provided | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1282 of the LRP5 protein (p.Gly1282Ser). This variant is present in population databases (rs747015625, gnomAD 0.01%). 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: 943061). 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 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. |
| Johns Hopkins Genomics, |
RCV001263477 | SCV001441558 | uncertain significance | Polycystic liver disease 4 with or without kidney cysts | 2020-10-22 | criteria provided, single submitter | clinical testing | This LRP5 variant (rs747015625) is rare (<0.1%) in a large population dataset (gnomAD: 4/249954 total alleles; 0.002%; no homozygotes) and has not been reported in the literature, to our knowledge. This variant has been reported in ClinVar. Of three bioinformatics tools queried, two predict that the substitution would be damaging, while one predicts that it would be tolerated. The glycine residue at this position is highly evolutionarily conserved across all species assessed. Due to insufficient evidence that this variant is deleterious, we consider the clinical significance of c.3844G>A to be uncertain at this time. |
| Breakthrough Genomics, |
RCV001213170 | SCV005190408 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
| Fulgent Genetics, |
RCV005005082 | SCV005630165 | 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 | 2024-05-23 | criteria provided, single submitter | clinical testing |