Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Seattle Children's Hospital Molecular Genetics Laboratory, |
RCV002254443 | SCV002525611 | likely pathogenic | not provided | 2021-04-23 | criteria provided, single submitter | clinical testing | The p.Tyr897Asn substitution has been reported as a somatic change in several individuals with blue rubber bleb nevus syndrome, both by itself (participant #12 in PMID: 27519652) and with a 2nd TEK substitution (PMID: 27519652). |
| Laboratory of Medical Genetics, |
RCV003314035 | SCV004013922 | likely pathogenic | Multiple cutaneous and mucosal venous malformations | 2023-06-13 | criteria provided, single submitter | clinical testing | PM2, PM5, PP3, PP5 |
| Clinical Genomics Laboratory, |
RCV003314035 | SCV005049535 | pathogenic | Multiple cutaneous and mucosal venous malformations | 2024-04-02 | criteria provided, single submitter | clinical testing | The TEK c.2689T>A (p.Tyr897Asn) variant was identified at an allelic fraction consistent with somatic origin. This variant has been reported in individuals affected with vascular malformation (Cao Y et al., 2023) and Blue Rubber Bleb Nevus (BRBN) Syndrome (Soblet J et al., PMID: 27519652). This variant has been reported in the ClinVar database as a likely pathogenic variant by two submitters (ClinVar ID: 1691345). This variant is absent from the general population (gnomAD v.4.0.0), indicating that it is not a common variant. Other variants in the same codon, c.2689T>C (p.Tyr897His), c.2690A>G (p.Tyr897Cys), have been reported in multiple individuals affected with venous malformations and are considered pathogenic (Cao Y et al., 2023; Ten Broek RW et al., PMID: 30677207; Limaye N et al., PMID: 26637981; Ye C et al., PMID: 21962923; Limaye N et al., PMID: 19079259; Soblet J et al., PMID: 27519652; Soblet J et al.; PMID: 23801934; Paolacci S et al., PMID: 33105631. The TEK c.2689T>A (p.Tyr897Asn) variant resides within the tyrosine kinase domain of TEK, which is a critical functional domain (Shewchuk LM et al., PMID: 11080633). Computational predictors indicate that the variant is damaging, evidence that may correlate with impact on TEK function. Based on an internally-developed protocol informed by the ACMG/AMP guidelines (Richards S et al., PMID: 25741868), the TEK c.2689T>A (p.Tyr897Asn) variant is classified as pathogenic. |