ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.1208T>C (p.Phe403Ser)

dbSNP: rs1830433526
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001058168 SCV001222717 likely pathogenic Hereditary hemorrhagic telangiectasia 2021-06-21 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ENG protein function (PMID: 22022569). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ENG protein function. This variant has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (Invitae). ClinVar contains an entry for this variant (Variation ID: 853374). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 403 of the ENG protein (p.Phe403Ser). The phenylalanine residue is moderately conserved and there is a large physicochemical difference between phenylalanine and serine.
Genetic Services Laboratory, University of Chicago RCV001819781 SCV002069197 uncertain significance not specified 2018-06-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV002348428 SCV002648509 likely pathogenic Cardiovascular phenotype 2020-11-30 criteria provided, single submitter clinical testing The p.F403S variant (also known as c.1208T>C), located in coding exon 9 of the ENG gene, results from a T to C substitution at nucleotide position 1208. The phenylalanine at codon 403 is replaced by serine, an amino acid with highly dissimilar properties. This alteration has previously been reported in a family with HHT (Prigoda NL et al. J. Med. Genet., 2006 Sep;43:722-8). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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.