Submissions for variant NM_002335.4(LRP5):c.1828G>A (p.Gly610Arg)

dbSNP: rs80358313

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001579335	SCV003440339	pathogenic	not provided	2025-01-18	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 610 of the LRP5 protein (p.Gly610Arg). This variant is present in population databases (rs80358313, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal dominant osteoporosis with retinopathy and autosomal recessive osteoporosis-pseudoglioma syndrome (PMID: 15981244, 16252235, 20340138). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 6294). 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 expected to disrupt LRP5 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects LRP5 function (PMID: 16252235). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004814848	SCV005071463	likely pathogenic	Retinal dystrophy	2022-01-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001579335	SCV005414733	uncertain significance	not provided	2024-05-12	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); 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: 31589614, 28191890, 15981244, 31785789, 35982159, 20340138, 31964843, 35982160, 35770050, 28714951, 36018796)
OMIM	RCV000006674	SCV000026857	pathogenic	Exudative vitreoretinopathy 4, autosomal recessive	2005-08-01	no assertion criteria provided	literature only
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579335	SCV001806838	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001579335	SCV001953563	likely pathogenic	not provided		no assertion criteria provided	clinical testing