ClinVar Miner

Submissions for variant NM_002335.4(LRP5):c.3337C>T (p.Arg1113Cys)

gnomAD frequency: 0.00006  dbSNP: rs377258285
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001062922 SCV001227748 uncertain significance not provided 2024-10-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1113 of the LRP5 protein (p.Arg1113Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with osteoporosis-pseudoglioma syndrome (PMID: 16252235). ClinVar contains an entry for this variant (Variation ID: 857281). 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) has been performed 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. 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.
GeneDx RCV001062922 SCV001788717 uncertain significance not provided 2020-03-02 criteria provided, single submitter clinical testing Observed in cis with two other LRP5 variants in a patient with osteoporosis-pseudoglioma syndrome in published literature (Ai et al., 2005); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16252235)
Fulgent Genetics, Fulgent Genetics RCV002505637 SCV002815868 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 2021-12-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003898070 SCV004716103 uncertain significance LRP5-related disorder 2023-12-20 no assertion criteria provided clinical testing The LRP5 c.3337C>T variant is predicted to result in the amino acid substitution p.Arg1113Cys. This variant in the compound heterozygous condition along with a second variant in this gene was reported in an individual with Osteoporosis-pseudoglioma syndrome (Ai et al 2005. PubMed ID: 16252235). This variant is reported in 0.010% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-68192670-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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