ClinVar Miner

Submissions for variant NM_000501.4(ELN):c.1324C>T (p.Gln442Ter) (rs137854452)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255419 SCV000321600 pathogenic not provided 2018-10-05 criteria provided, single submitter clinical testing The Q442X nonsense variant in the ELN gene has been reported previously in at least four unrelated individuals with supravalvular aortic stenosis (SVAS) (Li et al., 1997; Tassabehji et al., 1997; Metcalfe et al., 2000). Two of these individuals had additional diagnoses including peripheral pulmonary artery stenosis either in isolation or in combination with pulmonary artery stenosis and aortic hypoplasia (Metcalfe et al., 2000). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the ELN gene have been reported in the Human Gene Mutation Database in association with SVAS and pulmonary artery stenosis (Stenson et al., 2014). Furthermore, the Q442X variant is not observed in large population cohorts (Lek et al., 2016; Exome Variant Server).
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000018206 SCV000204236 pathogenic Supravalvar aortic stenosis 2011-08-04 criteria provided, single submitter clinical testing The Gln442X variant has been reported in 4 individuals with both sporadic and fa milial SVAS (Li 1997, Metcalfe 2000). In addition, this variant was absent from over 750 control chromosomes (Li 1997), supporting a pathogenic role. Furthermor e, the Gln442X variant it leads to a premature stop at codon 442 and is predicte d to lead to a truncated or absent protein. Loss of function is an established mechanism of disease for the ELN gene (Human Gene Mutation Database, HGMD). Ther efore, the Gln442X variant meets our criteria for pathogenicity (http://pcpgm.pa rtners.org/lmm) and is highly likely to be pathogenic.
OMIM RCV000018206 SCV000038485 pathogenic Supravalvar aortic stenosis 2000-12-01 no assertion criteria provided literature only

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