ClinVar Miner

Submissions for variant NM_000501.4(ELN):c.1928_1952del (p.Gly643fs) (rs863223524)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197740 SCV000250060 pathogenic not provided 2015-04-14 criteria provided, single submitter clinical testing The c.1928_1952del25 mutation in the ELN gene, denoted as c.2114_2138del25 due to a difference in nomenclature, has been previously published in association with cutis laxa and aortic aneurysm (Szabo et al., 2006). The c.1928_1952del25 mutation causes a frameshift starting with codon Glycine 643, changes this amino acid to a Glutamic Acid residue and creates a premature Stop codon at position 36 of the new reading frame, denoted p.Gly643GlufsX36. Expression studies have shown that the c.2114_2138del25 (c.1928_1952del25) mutation creates either a truncated protein product with a premature termination codon in exon 32 or an extended product lacking the sequence encoded by exon 32 as a result of normal alternative splicing but containing exons 30, 31, 33, 34 and part of the 3'-untranslated region of ELN (Szabo et al., 2006). Transgenic mice created using the elongated transcript were found to have severe respiratory distress, emphysema, abnormal lung mechanics, smaller size and higher mortality rate (Hu et al., 2010). Additionally, markers for TGF-beta signalling and the unfolded protein response were elevated and an increase in apoptosis was observed in the lungs of the mutant mice (Hu et al., 2010). Other frameshift mutations and gross deletions in the ELN gene have been reported in association with supravalvular aortic stenosis and cutis laxa. This variant was found in ELN

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.