ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.736del (p.Asp246fs) (rs1554810249)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522835 SCV000617304 pathogenic not provided 2017-09-18 criteria provided, single submitter clinical testing The c.736delG pathogenic variant in the ENG gene has previously been reported in a patient with epistaxis, telangiectases, and a pulmonary arteriovenous malformation (Cymerman et al., 2003). This variant has also been reported in another unrelated patient who met Curacao criteria for a diagnosis of HHT (reported as c.733delG due to use of alternative nomenclature) (Letteboer et al., 2005). The 736delG variant causes a shift in reading frame starting at codon aspartic acid 246, changing it to an isoleucine, and creating a premature stop codon at position 113 of the new reading frame, denoted p.Asp246IlefsX113. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other downstream frameshift variants in the ENG gene have been reported in Human Gene Mutation Database in association with HHT (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.736delG variant has not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
NIHR Bioresource Rare Diseases, University of Cambridge RCV001262068 SCV001439452 pathogenic Hereditary hemorrhagic telangiectasia type 1 2018-01-01 criteria provided, single submitter research PVS1+PM2+PP4

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