Submissions for variant NM_002335.4(LRP5):c.3279C>G (p.Ile1093Met)

gnomAD frequency: 0.00013  dbSNP: rs140852936

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001242947	SCV001416072	uncertain significance	not provided	2025-01-27	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1093 of the LRP5 protein (p.Ile1093Met). This variant is present in population databases (rs140852936, gnomAD 0.03%). 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: 967925). 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	RCV002499407	SCV002814312	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	2022-02-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002568562	SCV003676270	uncertain significance	Inborn genetic diseases	2021-10-12	criteria provided, single submitter	clinical testing	The c.3279C>G (p.I1093M) alteration is located in exon 15 (coding exon 15) of the LRP5 gene. This alteration results from a C to G substitution at nucleotide position 3279, causing the isoleucine (I) at amino acid position 1093 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV001242947	SCV005198686	uncertain significance	not provided	2023-11-01	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001242947	SCV005412393	uncertain significance	not provided	2023-09-06	criteria provided, single submitter	clinical testing	PP3