Submissions for variant NM_002334.4(LRP4):c.1765C>T (p.Arg589Cys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002622112	SCV002960988	uncertain significance	Cenani-Lenz syndactyly syndrome; Sclerosteosis 2; Congenital myasthenic syndrome 17	2022-11-08	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs768149014, gnomAD 0.003%). 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. 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 expected to disrupt LRP4 protein function. This variant has not been reported in the literature in individuals affected with LRP4-related conditions. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 589 of the LRP4 protein (p.Arg589Cys).
PreventionGenetics, part of Exact Sciences	RCV004738596	SCV005363044	uncertain significance	LRP4-related disorder	2024-06-17	no assertion criteria provided	clinical testing	The LRP4 c.1765C>T variant is predicted to result in the amino acid substitution p.Arg589Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% 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.