Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000171119 | SCV000223684 | uncertain significance | not provided | 2017-02-09 | criteria provided, single submitter | clinical testing | The Asn208Tyr variant in the SNTA1 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. Asn208Tyr results in a conservative amino acid substitution of a neutral, polar residue for another at a position that is not conserved across species. In silico analysis (PolyPhen2) predicts Asn208Tyr is benign to the protein structure/function (Adzhubei IA et al., 2010). Nevertheless, the Asn208Tyr variant was not detected in up to 600 alleles from control individuals of Caucasian and African American ancestry tested at GeneDx, indicating it is not a common benign variant in these populations. However, no mutations have been reported in nearby codons, which may indicate this region of the protein is tolerant of change. With the molecular and clinical information available, we cannot determine whether the Asn208Tyr variant is a disease-causing mutation or a rare benign variant. A pathogenic role of Asn208Tyr would be supported if it has occurred de novo in an individual or co-segregates with a LQTS phenotype in the family. The variant is found in LQT panel(s). |