ClinVar Miner

Submissions for variant NM_000501.4(ELN):c.295_296del (p.Ala99fs) (rs1554669297)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000627582 SCV000748582 likely pathogenic not provided 2018-04-09 criteria provided, single submitter clinical testing Although the c.295_296delGC likely pathogenic variant in the ELN gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon alanine 99, changing it to a cysteine, and creating a premature stop codon at position 5 of the new reading frame, denoted p.Ala99CysfsX5. This likely pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the ELN gene have been reported in Human Gene Mutation Database in association with ELN-related disorders (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.295_296delGC variant has not been observed in large population cohorts (Lek et al., 2016).
Invitae RCV000627823 SCV000748703 pathogenic Supravalvar aortic stenosis 2018-07-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala99Cysfs*5) in the ELN gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ELN-related disease. Loss-of-function variants in ELN are known to be pathogenic (PMID: 11175284). For these reasons, this variant has been classified as Pathogenic.

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.