Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001229612 | SCV001402064 | pathogenic | Hereditary hemorrhagic telangiectasia | 2021-03-26 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 956747). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with lysine at codon 190 of the ENG protein (p.Met190Lys). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and lysine. |
| Mayo Clinic Laboratories, |
RCV001508634 | SCV001714912 | uncertain significance | not provided | 2021-03-09 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002348772 | SCV002647879 | likely pathogenic | Cardiovascular phenotype | 2014-12-01 | criteria provided, single submitter | clinical testing | The p.M190K variant (also known as c.569T>A), located in coding exon 5 of the ENG gene, results from a T to A substitution at nucleotide position 569. The methionine at codon 190 is replaced by lysine, an amino acid with similar properties. In our internal cohort, this variant was detected in two individuals from one family with epistaxis and pulmonary arteriovenous malformations; one individual also had telangiectasias. In a second family in our internal cohort, this variant was found to track with epistaxis and/or pulmonary arteriovenous malformations in multiple individuals; telangiectasias were not reported in any of the symptomatic members of this family. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6489 samples (12978 alleles) with coverage at this position. 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 the majority of available evidence to date, this variant is likely to be pathogenic. |