Total submissions: 3
| 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, |
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. |