ClinVar Miner

Submissions for variant NM_000501.4(ELN):c.1858G>T (p.Gly620Ter) (rs727503034)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150645 SCV000197982 likely pathogenic Supravalvar aortic stenosis 2010-10-22 criteria provided, single submitter clinical testing The 1858G>T (Gly620X) variant has not been previously reported and is expected t o lead to heterozygous loss of function of the Elastin (ELN) gene by one or both of the following mechanisms. It creates a premature stop codon at position 620, which is predicted to lead to either truncated or absent protein (loss of funct ion). In addition, the 1858G>T variant affects the last base of exon 27, which i s part of the splicing consensus sequence and four computational tools predict t hat it severely affects splicing. Loss of function is an established mechanism of disease for the ELN gene (Human Genome Mutation Database, HGMD), which makes it highly likely that the 1858G>T variant is pathogenic.
Invitae RCV000150645 SCV001379615 pathogenic Supravalvar aortic stenosis 2019-10-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly682*) 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 conditions. ClinVar contains an entry for this variant (Variation ID: 163397). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in ELN are known to be pathogenic (PMID: 11175284). For these reasons, this variant has been classified as Pathogenic.

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