ClinVar Miner

Submissions for variant NM_002335.4(LRP5):c.1484G>A (p.Arg495His)

gnomAD frequency: 0.00001  dbSNP: rs200409162
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001243250 SCV001416396 uncertain significance not provided 2025-01-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 495 of the LRP5 protein (p.Arg495His). This variant is present in population databases (rs200409162, gnomAD 0.009%). 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: 968174). 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) 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.
Fulgent Genetics, Fulgent Genetics RCV002484342 SCV002791920 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 2021-09-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV004034746 SCV004899337 likely benign Inborn genetic diseases 2023-12-20 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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