Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000798666 | SCV000938292 | uncertain significance | Hypertrophic cardiomyopathy | 2022-09-23 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 56 of the TNNI3 protein (p.Ile56Thr). This variant is present in population databases (rs545441942, gnomAD 0.01%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 21533915, 27532257). ClinVar contains an entry for this variant (Variation ID: 165526). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Fulgent Genetics, |
RCV002483314 | SCV002785894 | uncertain significance | Dilated cardiomyopathy 2A; Cardiomyopathy, familial restrictive, 1; Dilated cardiomyopathy 1FF; Hypertrophic cardiomyopathy 7 | 2021-09-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003162619 | SCV003869211 | uncertain significance | Cardiovascular phenotype | 2022-12-13 | criteria provided, single submitter | clinical testing | The p.I56T variant (also known as c.167T>C), located in coding exon 5 of the TNNI3 gene, results from a T to C substitution at nucleotide position 167. The isoleucine at codon 56 is replaced by threonine, an amino acid with similar properties. This alteration has been reported in association with hypertrophic cardiomyopathy (HCM) (van den Wijngaard A et al. Neth Heart J, 2011 Aug;19:344-51; Alfares AA et al. Genet Med, 2015 Nov;17:880-8; Walsh R et al. Genet Med, 2017 Feb;19:192-203; Tadros R et al. Nat Genet, 2021 Feb;53:128-134). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Laboratory for Molecular Medicine, |
RCV000152091 | SCV000200737 | uncertain significance | not specified | 2013-01-30 | no assertion criteria provided | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |