Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000601198 | SCV000712293 | pathogenic | Supravalvar aortic stenosis | 2016-07-06 | criteria provided, single submitter | clinical testing | The p.Pro58fs variant in ELN has not been previously reported in individuals wit h congenital heart disease or in large population studies. This variant is predi cted to cause a frameshift, which alters the protein?s amino acid sequence begin ning at position 58 and leads to a premature termination codon 64 amino acids do wnstream. This alteration is then predicted to lead to a truncated or absent pro tein. Heterozygous loss of function of the ELN gene is an established disease me chanism in SVAS. In summary, the p.Pro58fs variant meets our criteria to be clas sified as pathogenic for SVAS in an autosomal dominant manner (http://pcpgm.part ners.org/lmm). |
| Invitae | RCV000601198 | SCV001205361 | pathogenic | Supravalvar aortic stenosis | 2019-11-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ELN are known to be pathogenic (PMID: 11175284). This variant has not been reported in the literature in individuals with ELN-related conditions. ClinVar contains an entry for this variant (Variation ID: 505162). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Pro58Leufs*64) in the ELN gene. It is expected to result in an absent or disrupted protein product. |