Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clinical Genomics Laboratory, |
RCV004562117 | SCV005049538 | pathogenic | Multiple cutaneous and mucosal venous malformations | 2023-12-20 | criteria provided, single submitter | clinical testing | A TEK c.3343G>T (p.Gly1115Ter) variant was identified at an allelic fraction consistent with somatic origin. This variant has been reported in sporadic venous malformations (Soblet J et al., PMID: 23801934). This variant is absent from the general population database (gnomAD v.4.0.0), indicating it is not a common variant. The TEK c.3343G>T (p.Gly1115Ter) variant causes a premature termination codon; however, because this occurs in the last exon, it is not predicted to lead to nonsense-mediated decay. This variant resides within the C-terminal tail, amino acids 905-A1124, of TEK, which is a critical functional region (Shewchuk LM et al., PMID: 11080633). Functional studies have demonstrated that this variant results in the truncation of the C-terminal inhibitory loop, leading to increased receptor autophosphorylation, indicating that this variant impacts protein function (Natynki M et al., PMID: 26319232). Based on an internally-developed protocol informed by the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the TEK c.3343G>T (p.Gly1115Ter) variant is classified as pathogenic. |
| MAGI's Lab - |
RCV001327977 | SCV001437653 | pathogenic | Abnormal cardiovascular system morphology | no assertion criteria provided | provider interpretation |