ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.1121_1124del (p.Lys374fs) (rs1064793734)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484786 SCV000566897 pathogenic not provided 2015-06-12 criteria provided, single submitter clinical testing The c.1121_1124delAAGA deletion in the ENG gene has been reported previously (reported asc.1120_1123 delAAAG due to alternate nomenclature) in one Japanese family with HHT (Dakeishi M etal., 2002). Furthermore, the c.1121_1124delAAGA variant was not observed in approximately 6,500individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. This deletion is expected to result in either anabnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNAdecay. Other frameshift variants in the ENG gene have been reported in HGMD in association withHHT (Stenson P et al., 2014). In summary, c.1121_1124delAAGA in the ENG gene is interpreted as a pathogenic variant.
Invitae RCV000530282 SCV000629543 pathogenic Hereditary hemorrhagic telangiectasia 2020-03-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys374Serfs*6) 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 individuals affected with hereditary hemorrhagic telangiectasia (PMID: 11793473, 20501893, Invitae). This variant is also known as c.1120_1123delAAAG in the literature. ClinVar contains an entry for this variant (Variation ID: 419225). 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.

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