ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs746136135
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae 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

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