ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.771dup (p.Tyr258fs) (rs1588581902)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002073 SCV001159910 pathogenic Hereditary hemorrhagic telangiectasia type 1 2018-09-06 criteria provided, single submitter clinical testing The ENG c.771dupC; p.Tyr258fs variant has been previously reported in at least one patient affected with hereditary hemorrhagic telangiectasia (HHT) (Lesca 2004). This variant is absent from general population databases (1000 Genome Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant creates a frameshift by duplicating a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Lesca G et al. Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France. Hum Mutat. 2004 Apr;23(4):289-99.
Invitae RCV001383204 SCV001582283 pathogenic Hereditary hemorrhagic telangiectasia 2020-08-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr258Leufs*76) 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 individual(s) with hereditary hemorrhagic telangiectasia (PMID: 16429404, 18673552). ClinVar contains an entry for this variant (Variation ID: 811750). Loss-of-function variants in ENG are known to be pathogenic (PMID: 15879500). For these reasons, this variant has been classified as Pathogenic.

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