ClinVar Miner

Submissions for variant NM_002335.4(LRP5):c.1132A>G (p.Ile378Val)

gnomAD frequency: 0.00008  dbSNP: rs369747444
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001057386 SCV001221875 uncertain significance not provided 2024-10-03 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 378 of the LRP5 protein (p.Ile378Val). This variant is present in population databases (rs369747444, gnomAD 0.01%). 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: 852712). 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 RCV005005015 SCV002814959 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 2024-02-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002553830 SCV003627032 uncertain significance Inborn genetic diseases 2022-07-14 criteria provided, single submitter clinical testing The c.1132A>G (p.I378V) alteration is located in exon 6 (coding exon 6) of the LRP5 gene. This alteration results from a A to G substitution at nucleotide position 1132, causing the isoleucine (I) at amino acid position 378 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.