ClinVar Miner

Submissions for variant NM_000459.5(TEK):c.3314_3315delinsTGACCT (p.Thr1105fs)

dbSNP: rs2131267739
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital RCV001533001 SCV001745388 likely pathogenic Venous malformation 2021-07-06 criteria provided, single submitter clinical testing A likely pathogenic variant was identified in the TEK gene: NM_000459:c.3314_3315delCCinsTGACCT, resulting in p.T1105Mfs*6. This variant was identified in ~10% of reads (n=1285), consistent with somatic origin. This variant leads to the insertion of a premature stop codon within the last exon (exon 23) of the TEK gene, and is predicted to escape nonsense mediated decay. Although this variant has not been previously reported, we classify it is as likely pathogenic. It is absent from large population databases (gnomAD v2.1), and multiple computational tools predict a deleterious effect. Late truncating mutations in TEK, similar but not identical to the p.T1105Mfs*6 variant, have been reported in individuals with sporadic venous malformations (PMID: 23801934), and functional studies of C-terminal truncating mutations have been shown to lead to ligand-independent kinase activation (PMID: 23801934, 12082108).

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