ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.142C>T (p.Gln48Ter)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001206409 SCV001377717 pathogenic Hereditary hemorrhagic telangiectasia 2019-06-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln48*) 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 an individual affected with hereditary hemorrhagic telangiectasia (PMID: 15517393). 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286215 SCV001472747 pathogenic Hereditary hemorrhagic telangiectasia type 1 2019-07-29 criteria provided, single submitter clinical testing The ENG c.142C>T; p.Gln48Ter variant is reported in the literature in an individual with HHT (Letteboer 2005). This variant is absent from general population databases (Exome Variant Server, 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. Other nearby and downstream truncating variants are also reported in association with HHT and are pathogenic (Bayrak-Toydemir 2004, Bossler 2006). Based on available information, the p.Gln48Ter variant is considered to be pathogenic. REFERENCES Bayrak-Toydemir P et al. Hereditary hemorrhagic telangiectasia: an overview of diagnosis and management in the molecular era for clinicians. Genet Med. 2004 Jul-Aug;6(4):175-91. Bossler AD et al. Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype. Hum Mutat. 2006 Jul;27(7):667-75. Letteboer TG et al. Hereditary hemorrhagic telangiectasia: ENG and ALK-1 mutations in Dutch patients. Hum Genet. 2005 Jan;116(1-2):8-16.

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