ClinVar Miner

Submissions for variant NM_002335.4(LRP5):c.1304C>T (p.Thr435Met)

gnomAD frequency: 0.00001  dbSNP: rs777314081
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001075597 SCV001241224 uncertain significance Retinal dystrophy 2019-01-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001862623 SCV002287757 uncertain significance not provided 2025-01-18 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 435 of the LRP5 protein (p.Thr435Met). This variant is present in population databases (rs777314081, gnomAD 0.005%). 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: 867078). 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.
Fulgent Genetics, Fulgent Genetics RCV005005033 SCV002776602 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 2024-02-05 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001862623 SCV005412390 uncertain significance not provided 2024-08-13 criteria provided, single submitter clinical testing PP3, PM2
PreventionGenetics, part of Exact Sciences RCV004743285 SCV005362891 uncertain significance LRP5-related disorder 2024-08-27 no assertion criteria provided clinical testing The LRP5 c.1304C>T variant is predicted to result in the amino acid substitution p.Thr435Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0050% of alleles in individuals of East Asian descent in gnomAD. 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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