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Congenital Heart Defect v1.9 EGFR chirag patel Marked gene: EGFR as ready
Congenital Heart Defect v1.9 EGFR chirag patel Gene: egfr has been classified as Green List (High Evidence).
Congenital Heart Defect v1.9 chirag patel Copied gene EGFR from panel Mendeliome
Congenital Heart Defect v1.9 EGFR chirag patel gene: EGFR was added
gene: EGFR was added to Congenital Heart Defect. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: EGFR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EGFR were set to 24691054,36017778,26436111,32250467,32602142,40040597,29899996,9176390,7618085,7630400
Phenotypes for gene: EGFR were set to Inflammatory skin and bowel disease, neonatal 2, MONDO:0014481
Congenital Heart Defect v0.367 KDR Zornitza Stark edited their review of gene: KDR: Added comment: PMID 34113005: Exome sequencing in a family with two siblings affected by ToF revealed biallelic missense variants in KDR. Studies in knock-in mice and in HEK 293T cells identified embryonic lethality for one variant when occurring in the homozygous state, and a significantly reduced VEGFR2 phosphorylation for both variants.

Rare variant burden analysis conducted in a set of 1,569 patients of European descent with ToF identified a 46-fold enrichment of protein-truncating variants (PTVs) in TOF cases compared to controls (P = 7 × 10-11).

At this stage MOI unclear and insufficient evidence for either MOI.; Changed rating: AMBER; Changed publications: 34113005; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital Heart Defect v0.239 KDR Chloe Stutterd gene: KDR was added
gene: KDR was added to Congenital Heart Defect. Sources: Literature,Expert list
Mode of inheritance for gene: KDR was set to Unknown
Publications for gene: KDR were set to 34113005; 34328347; 30232381
Phenotypes for gene: KDR were set to Tetralogy of Fallot
Review for gene: KDR was set to RED
gene: KDR was marked as current diagnostic
Added comment: Rare variants associated with ToF but lacking evidence for causality and pathogenesis.

PMID 34113005 (2021): Exome sequencing in a family with two siblings affected by TOF revealed biallelic missense variants in KDR. Studies in knock-in mice and in HEK 293T cells identified embryonic lethality for one variant when occurring in the homozygous state, and a significantly reduced VEGFR2 phosphorylation for both variants. Rare variant burden analysis conducted in a set of 1,569 patients of European descent with TOF identified a 46-fold enrichment of protein-truncating variants (PTVs) in TOF cases compared to controls (P = 7 × 10-11).

PMID 34328347 (2021): exome sequencing data from 811 probands with ToF, four patients had novel LoF variants in KDR demonstrating enrichment in ToF compared with controls. Segregation data not available.

PMID: 30232381 (2019): KDR variants identified in four patients (two stopgain and two nonsynonymous variants) with other VUS identified in one patient. Segregation data not available.
Sources: Literature, Expert list