ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1583C>A (p.Thr528Lys) (rs57629361)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000057328 SCV000233099 pathogenic not provided 2017-01-03 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000201062 SCV000255783 likely pathogenic Emery-Dreifuss muscular dystrophy 2, autosomal dominant 2015-06-26 criteria provided, single submitter clinical testing
Mendelics RCV000986432 SCV001135432 likely pathogenic Hutchinson-Gilford syndrome 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001045262 SCV001209102 pathogenic Charcot-Marie-Tooth disease, type 2 2019-01-30 criteria provided, single submitter clinical testing This sequence change replaces threonine with lysine at codon 528 of the LMNA protein (p.Thr528Lys). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with LMNA-related disesae (PMID: 10739764, 20980393, 24642510). ClinVar contains an entry for this variant (Variation ID: 66849). This variant has been reported to affect LMNA protein function (PMID: 23427149, 21173262). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Thr528 amino acid residue in LMNA. Other variant(s) that disrupt this residue (p.Thr528Arg) have been observed in individuals with LMNA-related conditions (PMID: 14684700, 20376791, 26165385), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Epithelial Biology; Institute of Medical Biology, Singapore RCV000057328 SCV000088441 not provided not provided no assertion provided not provided

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.