Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000460714 | SCV000546115 | pathogenic | Hereditary hemorrhagic telangiectasia | 2025-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 238 of the ENG protein (p.Val238Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of hereditary hemorrhagic telangiectasia (PMID: 20414677; internal data). ClinVar contains an entry for this variant (Variation ID: 407121). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ENG protein function. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001753879 | SCV001985405 | uncertain significance | not provided | 2024-08-22 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20414677) |
| Ambry Genetics | RCV002365627 | SCV002665494 | uncertain significance | Cardiovascular phenotype | 2018-09-05 | criteria provided, single submitter | clinical testing | The p.V238E variant (also known as c.713T>A), located in coding exon 6 of the ENG gene, results from a T to A substitution at nucleotide position 713. The valine at codon 238 is replaced by glutamic acid, an amino acid with dissimilar properties. This alteration was described in individual with possible hereditary hemorrhagic telangiectasia based on pulmonary AVMs and a family history. Reportedly, the alteration segregated with disease in the family; however, the number of family members, clinical information on additional relatives, and the nature of the familial relationships were not described (Richards-Yutz J et al. Hum. Genet., 2010 Jul;128:61-77). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Mayo Clinic Laboratories, |
RCV001753879 | SCV004226817 | likely pathogenic | not provided | 2022-10-12 | criteria provided, single submitter | clinical testing | PP1_strong, PM2_supporting, PS4_moderate |