ClinVar Miner

Submissions for variant NM_002335.4(LRP5):c.425G>A (p.Arg142Gln)

gnomAD frequency: 0.00001  dbSNP: rs368198391
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001240856 SCV001413833 likely pathogenic not provided 2023-11-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 142 of the LRP5 protein (p.Arg142Gln). This variant is present in population databases (rs368198391, gnomAD 0.02%). This missense change has been observed in individuals with clinical features of autosomal dominant exudative vitreoretinopathy (PMID: 28192794; Invitae). ClinVar contains an entry for this variant (Variation ID: 966231). 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. This variant disrupts the p.Arg142 amino acid residue in LRP5. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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, Fulgent Genetics RCV002480801 SCV002787120 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 2022-05-16 criteria provided, single submitter clinical testing

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