Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
SIB Swiss Institute of Bioinformatics | RCV000852314 | SCV000994949 | uncertain significance | Capillary malformation-arteriovenous malformation 2 | 2019-03-29 | criteria provided, single submitter | curation | This variant is interpreted as Uncertain significance for Capillary malformation-arteriovenous malformation 2. The following ACMG Tag(s) were applied: PP3: Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM2-Supporting: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM1: Located in a mutational hot spot and/or critical and well-established functional domain (e.g.,active site of an enzyme) without benign variation. |
Invitae | RCV003558617 | SCV004294527 | pathogenic | not provided | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 807 of the EPHB4 protein (p.Gly807Arg). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of capillary malformation-arteriovenous malformation (PMID: 28687708, 36813543; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 691539). 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 EPHB4 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |