ClinVar Miner

Submissions for variant NM_002335.4(LRP5):c.3404G>A (p.Arg1135His)

dbSNP: rs560826688
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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 RCV002051383 SCV002111522 uncertain significance not provided 2023-05-08 criteria provided, single submitter clinical testing This variant is present in population databases (rs560826688, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1135 of the LRP5 protein (p.Arg1135His). This missense change has been observed in individual(s) with clinical features of LRP5-related conditions (PMID: 29168297). ClinVar contains an entry for this variant (Variation ID: 1350710). 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. 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 RCV002503368 SCV002814093 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 2021-09-20 criteria provided, single submitter clinical testing
GeneDx RCV002051383 SCV004025717 uncertain significance not provided 2023-02-10 criteria provided, single submitter clinical testing Reported in a patient with single-suture craniosynostosis in published literature (Clarke et al., 2018); patient information is limited; Identified in a patient with clinical features of osteogenesis imperfecta in published literature (Bardai et al., 2017); limited clinical information provided; 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: 28378289, 29168297)
PreventionGenetics, part of Exact Sciences RCV004743595 SCV005361197 uncertain significance LRP5-related disorder 2024-08-15 no assertion criteria provided clinical testing The LRP5 c.3404G>A variant is predicted to result in the amino acid substitution p.Arg1135His. This variant has been reported in the heterozygous state in an individual with craniosynostosis (Clarke et al. 2018. PubMed ID: 29168297). This variant is reported in 0.0085% of alleles in individuals of Latino 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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