Submissions for variant NM_002334.4(LRP4):c.4544G>C (p.Gly1515Ala)

gnomAD frequency: 0.00001  dbSNP: rs758635404

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000816928	SCV000957457	uncertain significance	Cenani-Lenz syndactyly syndrome; Sclerosteosis 2; Congenital myasthenic syndrome 17	2018-12-18	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with LRP4-related conditions. This variant is present in population databases (rs758635404, ExAC 0.009%). This sequence change replaces glycine with alanine at codon 1515 of the LRP4 protein (p.Gly1515Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine.
PreventionGenetics, part of Exact Sciences	RCV004528311	SCV004108063	uncertain significance	LRP4-related disorder	2023-06-13	criteria provided, single submitter	clinical testing	The LRP4 c.4544G>C variant is predicted to result in the amino acid substitution p.Gly1515Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-46894690-C-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.