ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.398G>C (p.Arg133Pro) (rs60864230)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000686691 SCV000814219 uncertain significance Charcot-Marie-Tooth disease, type 2 2019-05-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 133 of the LMNA protein (p.Arg133Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Emery-Dreifuss muscular dystrophy (PMID: 11503164) . ClinVar contains an entry for this variant (Variation ID: 14508). Experimental studies have shown that this missense change affects protein function (PMID: 16218190). Variants that disrupt the p.Arg133Leu, p.Arg133Gln, amino acid residue in LMNA have been observed in affected individuals (PMID: 12629077, 12927431, 14615128, 16174718). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. 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.
OMIM RCV000015602 SCV000035867 pathogenic Emery-Dreifuss muscular dystrophy 2, autosomal dominant 2003-08-09 no assertion criteria provided literature only
Epithelial Biology; Institute of Medical Biology, Singapore RCV000057398 SCV000088511 not provided not provided no assertion provided not provided

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