ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.586T>C (p.Trp196Arg)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital RCV001533004 SCV001745384 likely pathogenic Hereditary hemorrhagic telangiectasia 2021-07-06 criteria provided, single submitter clinical testing A heterozygous, likely pathogenic variant was identified in exon 5 of the ENG gene (NM_000118.3:c.586T>C, p.Trp196Arg). This variant has previously been reported to segregate in a single family with multiple individuals with HHT. This variant has not been observed in the Genome Aggregation Database (v2.1.1). The substitution of tryptophan with arginine at position 196 is predicted to be damaging to protein function (SIFT, PROVEAN, Mutation assessor, FATHMM-MKL). This variant falls within the orphan region (OR) 2 domain of ENG that binds bone morphogenetic protein 9 (BMP9). Nearby substitutions have been reported as pathogenic, thus taken together, this variant is located in a critical domain (ACMG criteria PM1). Pathogenic variants in ENG cause the autosomal dominant disorder HHT type 1. HHT is characterized by telangiectasias, recurrent spontaneous nosebleeds (epistaxis), and arteriovenous malformations (AVMs).

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