Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001184655 | SCV001350682 | uncertain significance | Cardiomyopathy | 2019-08-07 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with cysteine at codon 39 of the TNNI3 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV001876150 | SCV002123621 | uncertain significance | Hypertrophic cardiomyopathy | 2020-11-15 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TNNI3-related conditions. ClinVar contains an entry for this variant (Variation ID: 923734). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with cysteine at codon 39 of the TNNI3 protein (p.Ser39Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. |