Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000701643 | SCV000830454 | likely pathogenic | Hypertrophic cardiomyopathy | 2018-09-04 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. A computational algorithm designed to assess the pathogenicity of variants in TNNI3 with regard to hypertrophic cardiomyopathy predicted this sequence change to be deleterious. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). This variant has been observed to be de novo in an individual affected with dilated cardiomyopathy (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 135 of the TNNI3 protein (p.Leu135Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. |