Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001289606 | SCV001477568 | uncertain significance | Telangiectasia, hereditary hemorrhagic, type 1 | 2019-10-17 | criteria provided, single submitter | clinical testing | The ENG c.1807G>A; p.Gly603Arg variant is reported in the literature in an individual with HHT (Richards-Yutz 2010). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The glycine at codon 603 is highly conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. This variant is predicted to create a cryptic splice acceptor site, which may alter splicing (Alamut v.2.11). Due to the limited information, the clinical significance of this variant is uncertain at this time. REFERENCES Richards-Yutz J et al. Update on molecular diagnosis of hereditary hemorrhagic telangiectasia. Hum Genet. 2010 Jul;128(1):61-77. |
Ambry Genetics | RCV002411932 | SCV002713205 | uncertain significance | Cardiovascular phenotype | 2019-08-29 | criteria provided, single submitter | clinical testing | The p.G603R variant (also known as c.1807G>A), located in coding exon 14 of the ENG gene, results from a G to A substitution at nucleotide position 1807. The glycine at codon 603 is replaced by arginine, an amino acid with dissimilar properties. This variant was identified in an individual with epistaxis, telangiectasias, and a family history (Richards-Yutz J et al. Hum. Genet., 2010 Jul;128:61-77). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on available evidence to date, the clinical significance of this alteration remains unclear. |
Invitae | RCV003594127 | SCV004296095 | likely pathogenic | Hereditary hemorrhagic telangiectasia | 2023-09-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 995600). This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 20414677). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 603 of the ENG protein (p.Gly603Arg). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |