ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.-127C>T (rs1060501408)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000463117 SCV000546104 pathogenic Hereditary hemorrhagic telangiectasia 2020-06-21 criteria provided, single submitter clinical testing This variant occurs in a non-coding region of the ENG gene. It does not change the encoded amino acid sequence of the ENG protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 21967607, 22192717, 28989145). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 407113). This variant has been reported to affect ENG protein function (PMID: 21967607, 22192717). For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756078 SCV000883794 pathogenic not provided 2018-03-16 criteria provided, single submitter clinical testing The ENG c.-127C>T variant (rs1060501408) has been reported to segregate with disease in families affected with hereditary hemorrhagic telangiectasia (HHT) (Damjanovich 2011, Kim 2011). This variant is reported as pathogenic in ClinVar (Variation ID: 407113) and is absent from general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. In vitro functional analyses of this variant demonstrate generation of an aberrant translational start codon and decreased endoglin expression (Damjanovich 2011, Kim 2011). Based on the above information, this variant is considered pathogenic. References: Damjanovich K et al. 5'UTR mutations of ENG cause hereditary hemorrhagic telangiectasia. Orphanet J Rare Dis. 2011 Dec 22;6:85. Kim M et al. Clinical and genetic analyses of three Korean families with hereditary hemorrhagic telangiectasia. BMC Med Genet. 2011 Oct 3;12:130.
NIHR Bioresource Rare Diseases, University of Cambridge RCV001262048 SCV001439426 likely pathogenic Hereditary hemorrhagic telangiectasia type 1 2018-01-01 criteria provided, single submitter research PM2+PP4+PP5
Mayo Clinic Laboratories, Mayo Clinic RCV000756078 SCV001714919 pathogenic not provided 2021-03-31 criteria provided, single submitter clinical testing PS3, PS4_Moderate, PM2_supporting, PP1_Strong

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