ClinVar Miner

Submissions for variant NM_004444.5(EPHB4):c.175G>A (p.Glu59Lys)

dbSNP: rs1584667224
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SIB Swiss Institute of Bioinformatics RCV000852310 SCV000994944 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: PM2: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3: Multiple lines of computational evidence support a deleterious effect on the gene or gene product.
GeneDx RCV001562165 SCV001784888 uncertain significance not provided 2024-04-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30819650, 28687708, Mishra[computational]2023)
Labcorp Genetics (formerly Invitae), Labcorp RCV001562165 SCV002215649 uncertain significance not provided 2024-11-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 59 of the EPHB4 protein (p.Glu59Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with capillary malformation-arteriovenous malformation (PMID: 28687708). ClinVar contains an entry for this variant (Variation ID: 691535). 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) indicates that this missense variant is not expected to disrupt EPHB4 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital RCV001562165 SCV002525693 pathogenic not provided 2021-12-02 criteria provided, single submitter clinical testing The p.Glu59Lys variant has been previously reported in the literature and in patient databases (PMID: 28687708). This variant substitutes a glutamic acid at amino acid position 59 with a lysine in the ligand-binding domain of the EPHB4 protein and is absent from the general population (gnomAD v.2.1.1).

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