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

gnomAD frequency: 0.00001  dbSNP: rs1554809450

Total submissions: 6

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