Submissions for variant NM_001114753.3(ENG):c.1550_1551del (p.Val517fs)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000197179	SCV000250088	pathogenic	not provided	2014-07-07	criteria provided, single submitter	clinical testing	The c.1550_1551delTG mutation in the ENG gene has been reported previously in association with HHT (McAllister K et al., 1995; Olivieri C et al., 2007). The c.1550_1551delTG mutation was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This mutation causes a shift in reading frame starting at codon Valine 517, changing it to a Glutamic acid, and creating a premature stop codon at position 10 of the new reading frame, denoted p.Val517GlufsX10. This mutation is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift mutations in the ENG gene have been reported in association with HHT. In summary, c.1550_1551delTG in the ENG gene is interpreted as a disease-causing mutation.
Mayo Clinic Laboratories, Mayo Clinic	RCV000197179	SCV002103221	pathogenic	not provided	2021-07-20	criteria provided, single submitter	clinical testing	PVS1, PS4_moderate, PM2
Labcorp Genetics (formerly Invitae), Labcorp	RCV002517174	SCV003441298	pathogenic	Hereditary hemorrhagic telangiectasia	2022-05-29	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 213215). This premature translational stop signal has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 8595426, 24603890). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val517Glufs*10) in the ENG gene. It is expected to result in an absent or disrupted protein product. 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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