ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.360C>A (p.Tyr120Ter) (rs121918402)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000018156 SCV001157143 pathogenic Hereditary hemorrhagic telangiectasia type 1 2018-10-08 criteria provided, single submitter clinical testing The ENG c.360C>A; p.Tyr120Ter variant (rs121918402), is reported in the literature in multiple individuals and families affected with hereditary hemorrhagic telangiectasia (Brusgaard 2004, Kjeldsen 2005, Torring 2014). This variant is reported in ClinVar (Variation ID: 16676), and is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, the p.Tyr120Ter variant is considered to be pathogenic. References: Brusgaard K et al. Mutations in endoglin and in activin receptor-like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia. Clin Genet. 2004 Dec;66(6):556-61. Kjeldsen AD et al. Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia. J Intern Med. 2005 Oct;258(4):349-55. Torring PM et al. National mutation study among Danish patients with hereditary haemorrhagic telangiectasia. Clin Genet. 2014 Aug;86(2):123-33.
Invitae RCV001212827 SCV001384425 pathogenic Hereditary hemorrhagic telangiectasia 2019-06-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr120*) in the ENG 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 been observed in several individuals affected with hereditary hemorrhagic telangiectasia (PMID: 15521985). ClinVar contains an entry for this variant (Variation ID: 16676). 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 ENG are known to be pathogenic (PMID: 15879500, 20656886, 22385575). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000018156 SCV000038435 pathogenic Hereditary hemorrhagic telangiectasia type 1 2004-12-01 no assertion criteria provided literature only

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