ClinVar Miner

Submissions for variant NM_000501.4(ELN):c.2T>C (p.Met1Thr)

dbSNP: rs863223518
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000195606 SCV000250053 pathogenic not provided 2023-02-09 criteria provided, single submitter clinical testing Initiation codon variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35741248, 28574231, 22740173)
Invitae RCV000627831 SCV000748711 pathogenic Supravalvar aortic stenosis 2023-10-03 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the ELN mRNA. There are no downstream in-frame methionine residues; therefore, it is expected to result in an absent or disrupted protein product. Loss-of-function variants in ELN are known to be pathogenic (PMID: 9215670, 11175284). This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with syndromic structural heart defects (PMID: 10942104, 22740173). ClinVar contains an entry for this variant (Variation ID: 213185). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000627831 SCV004848463 likely pathogenic Supravalvar aortic stenosis 2020-08-24 criteria provided, single submitter clinical testing The p.Met1? in ELN has been reported in 2 family members with peripheral pulmonary stenosis, supravalvular aortic stenosis, and severe pulmonary emphysema (Louw 2012 PubMed: 22740173) and was absent from large population studies. This variant is listed in ClinVar (allele ID: 209907). This variant affects the translation initiation start codon (ATG). Since no other in-frame methionine is present in the elastin mRNA, this variant is predicted to lead to the absence of the elastin protein. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP Criteria applied: PM2, PVS1_Strong, PS4_Supporting.

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