ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.1346_1347del (p.Ser449fs)

dbSNP: rs1564453019
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002233257 SCV000822351 pathogenic Hereditary hemorrhagic telangiectasia 2021-04-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ENG are known to be pathogenic (PMID: 15879500, 20656886, 22385575). This variant has been observed in several individuals affected with hereditary hemorrhagic telangiectasia (PMID: 12673790, 15024723, 15517393, 22991266). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser449Phefs*51) in the ENG gene. It is expected to result in an absent or disrupted protein product.
Mayo Clinic Laboratories, Mayo Clinic RCV001507759 SCV001713505 pathogenic not provided 2019-09-23 criteria provided, single submitter clinical testing PVS1, PM2, PS4_Moderate, PP4
GeneDx RCV001507759 SCV002538893 pathogenic not provided 2022-06-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Frameshift 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: 22991266, 15879500, 23801935, 15880681, 15517393, 15024723, 32300199, 12673790, 15907823, 16470787)
Ambry Genetics RCV002386207 SCV002693309 pathogenic Cardiovascular phenotype 2019-05-08 criteria provided, single submitter clinical testing The c.1346_1347delCT pathogenic mutation, located in coding exon 11 of the ENG gene, results from a deletion of two nucleotides at nucleotide positions 1346 to 1347, causing a translational frameshift with a predicted alternate stop codon (p.S449Ffs*51). This mutation was first described in a hereditary hemorrhagic telangiectasia (HHT) family with multiple affected individuals; the proband had reduced levels of endoglin compared to controls (Cymerman U et al. Hum. Mutat., 2003 May;21:482-92). This mutation has also been described in French, Dutch, and German individuals with HHT (Lesca G et al. Hum. Mutat., 2004 Apr;23:289-99; Letteboer TG et al. Hum. Genet., 2005 Jan;116:8-16; Schulte C et al. Hum. Mutat., 2005 Jun;25:595). 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.

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.