Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000255722 | SCV000322239 | pathogenic | not provided | 2016-08-17 | criteria provided, single submitter | clinical testing | The Y150X pathogenic variant in the ELN gene has been reported previously in a female proband and her brother, both with mild supravalvular aortic stenosis (SVAS), as well as her son who exhibited severe SVAS, supravalvular pulmonary stenosis, and peripheral pulmonary artery stenosis (Metcalfe et al., 2000). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Y150X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret Y150X as a pathogenic variant. |
Invitae | RCV002518760 | SCV003440033 | pathogenic | Supravalvar aortic stenosis | 2023-11-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr150*) in the ELN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ELN are known to be pathogenic (PMID: 11175284). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with supravalvular aortic stenosis (PMID: 11175284). ClinVar contains an entry for this variant (Variation ID: 265394). For these reasons, this variant has been classified as Pathogenic. |