ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.1306C>T (p.Gln436Ter)

gnomAD frequency: 0.00001  dbSNP: rs1554809450
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506337 SCV000603478 pathogenic not provided 2017-05-23 criteria provided, single submitter clinical testing The ENG c.1306C>T, p.Gln436Ter variant has been reported in a patient diagnosed with hereditary hemorrhagic telangiectasia (Lenato 2006). It is not listed in the dbSNP variant database, nor observed in the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database). The variant introduces a premature termination codon, and is predicted to result in a truncated protein or an absent transcript. Based on the above information, the variant is classified as pathogenic. References: Lenato G et al. DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population. Hum Mutat. 2006; 27(2):213-4.
Invitae RCV001212134 SCV001383710 pathogenic Hereditary hemorrhagic telangiectasia 2023-10-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln436*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with hereditary hemorrhagic telangiectasia (PMID: 16429404, 21158752). ClinVar contains an entry for this variant (Variation ID: 439662). For these reasons, this variant has been classified as Pathogenic.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000512687 SCV001439484 pathogenic Telangiectasia, hereditary hemorrhagic, type 1 2018-01-01 criteria provided, single submitter research PVS1+PM2+PP4
GeneDx RCV000506337 SCV002520278 pathogenic not provided 2021-11-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 31220907, 32573726, 21158752, 16429404)
Ambry Genetics RCV002383980 SCV002693763 pathogenic Cardiovascular phenotype 2019-01-28 criteria provided, single submitter clinical testing The p.Q436* pathogenic mutation (also known as c.1306C>T), located in coding exon 10 of the ENG gene, results from a C to T substitution at nucleotide position 1306. This changes the amino acid from a glutamine to a stop codon within coding exon 10. In one study, this alteration was detected in an individual with a clinical diagnosis of hereditary hemorrhagic telangiectasia (Lenato GM et al. Hum. Mutat., 2006 Feb;27:213-4). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Genetics, Medical University of Vienna RCV000512687 SCV000346039 likely pathogenic Telangiectasia, hereditary hemorrhagic, type 1 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.