Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000774233 | SCV000907934 | uncertain significance | Cardiomyopathy | 2023-06-14 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with methionine at codon 31 of the TNNI3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least one individual affected with hypertrophic cardiomyopathy (PMID: 33495597). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The 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 | RCV000812844 | SCV000953172 | uncertain significance | Hypertrophic cardiomyopathy | 2023-04-03 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 629524). This variant has not been reported in the literature in individuals affected with TNNI3-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 31 of the TNNI3 protein (p.Thr31Met). |
Ambry Genetics | RCV002370039 | SCV002686891 | uncertain significance | Cardiovascular phenotype | 2022-06-24 | criteria provided, single submitter | clinical testing | The p.T31M variant (also known as c.92C>T), located in coding exon 3 of the TNNI3 gene, results from a C to T substitution at nucleotide position 92. The threonine at codon 31 is replaced by methionine, an amino acid with similar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Harper AR et al. Nat Genet, 2021 02;53:135-142). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002477765 | SCV002794048 | uncertain significance | Dilated cardiomyopathy 2A; Cardiomyopathy, familial restrictive, 1; Dilated cardiomyopathy 1FF; Hypertrophic cardiomyopathy 7 | 2021-07-13 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000812844 | SCV004821895 | uncertain significance | Hypertrophic cardiomyopathy | 2024-01-11 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with methionine at codon 31 of the TNNI3 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not 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). The 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. |