ClinVar Miner

Submissions for variant NM_002334.4(LRP4):c.3830G>A (p.Arg1277His)

gnomAD frequency: 0.00001  dbSNP: rs746136135
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 RCV000691410 SCV000819188 uncertain significance Cenani-Lenz syndactyly syndrome; Sclerosteosis 2; Congenital myasthenic syndrome 17 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1277 of the LRP4 protein (p.Arg1277His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs746136135, ExAC 0.006%). This missense change has been observed in individual(s) with clinical features of congenital myasthenic syndrome (PMID: 24234652). ClinVar contains an entry for this variant (Variation ID: 189821). 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. Experimental studies have shown that this missense change affects LRP4 function (PMID: 24234652). 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.
Centogene AG - the Rare Disease Company RCV000170321 SCV002059484 uncertain significance Congenital myasthenic syndrome 17 2021-04-14 criteria provided, single submitter clinical testing
OMIM RCV000170321 SCV000222708 pathogenic Congenital myasthenic syndrome 17 2014-04-01 no assertion criteria provided literature only

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.