Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000159241 | SCV000209187 | uncertain significance | not provided | 2012-02-23 | criteria provided, single submitter | clinical testing | The Val188Leu variant in the TNNI3 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. Although Val188Leu results in a conservative amino acid substitution of one non-polar amino acid with another, the substitution occurs at a position that is conserved in mammalian species. Mutations in neighboring codons (Asn185Lys, Arg186Gln, Ile195Met, Asp196Asn) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. Additionally, the NHLBI ESP Exome Variant Server reports Val188Leu was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Nevertheless, multiple in silico analyses yield conflicting results regarding the effect of this variant on the protein structure/function.In summary, with the clinical and molecular information available at this time, we cannot unequivocally determine if the Val188Leu variant in the TNNI3 gene is a disease-causing mutation or a rare benign polymorphism.The variant is found in HCM panel(s). |