Mosaic skin disorders - deep sequencing

Gene: TEK

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 6 Dec 2024, 11:18 a.m. | Last Modified: 6 Dec 2024, 11:18 a.m.

Panel Version: 2.49

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Comment on list classification: Multiple cases of sporadic vascular malformations due to cutaneous mosaicism of a TEK variant (PMID: 19079259; 30677207; 34850385; 35460567; 35740480; 36924216). Different variants reported but the L914F substitution is most common and as are double variants found in cis. Somatic variants may not be picked up via other panels for the phenotype (R326) and therefore this gene should be promoted to Green at then next GMS panel update.

Created: 23 Aug 2023, 10:56 a.m. | Last Modified: 23 Aug 2023, 10:56 a.m.

Panel Version: 2.27

Green List (high evidence)

Multiple cutaneous and mucosal venous malformations (VMCM) and blue rubber bleb naevus (BRBN) usually caused by double variants in cis; commonly Y897C-R915C in VMCM and T1105N-T1106P in BRBN. Unifocal venous malformation association with single somatic hit, most commonly L914F.

Created: 5 May 2023, 2:19 p.m. | Last Modified: 5 May 2023, 2:19 p.m.

Panel Version: 2.1

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Blue rubber bleb naevus; multiple cutaneous and mucosal venous malformations (VMCM)

Publications

• PMID: 27519652

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

I don't know

As advised by Genomics England clinician - "TEK is currently green on vascular and DDG2P panels, activating germline mutations cause cutaneous mucosal venous malformations, somatic mutations cause blue rubber bleb naevus syndrome. I don’t know how much evidence there is for blood mosaicism detection (versus tissue testing). Soblet et al, 2017, (PMID 27519652), didn’t find the pathogenic variants (identified through tissue testing) with targeted deep sequencing in blue rubber bleb naevus syndrome, but did find one at the 1-5% level in sporadic multifocal vascular malformation (probably all related conditions??). As not much targeted deep sequencing has been done it’s possible this would be a good future one.
Sources: Expert Review

Created: 12 Dec 2019, 5:14 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Venous malformations, multiple cutaneous and mucosal, 600195

Publications

• 27519652