Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Agnes Ginges Centre for Molecular Cardiology, |
RCV000584812 | SCV000692526 | uncertain significance | Hypertrophic cardiomyopathy 1 | 2017-03-28 | criteria provided, single submitter | research | The TPM1 Glu212Val variant is present in the large Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/) as a singleton event and is absent in the 1000 genomes project (http://www.1000genomes.org/). We identified this variant in a HCM proband (IVS= 22mm) with no family history of disease. Computational tools SIFT, PolyPhen-2, PolyPhen-HCM and MutationTaster all predict this variant to have a deleterious effect. In summary, based on the limited available information and rarity in the general population, we classify TPM1 Glu212Val as a variant of "uncertain significance". |
Color Diagnostics, |
RCV001177697 | SCV001341953 | uncertain significance | Cardiomyopathy | 2020-02-25 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with valine at codon 212 of the TPM1 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 28408708). This variant has been identified in 1/251306 chromosomes 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 | RCV001860108 | SCV002140804 | uncertain significance | Hypertrophic cardiomyopathy | 2021-10-29 | 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 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 492989). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 28790153). This variant is present in population databases (rs769951937, gnomAD 0.006%). This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 212 of the TPM1 protein (p.Glu212Val). |
CHEO Genetics Diagnostic Laboratory, |
RCV001177697 | SCV003838407 | uncertain significance | Cardiomyopathy | 2022-02-25 | criteria provided, single submitter | clinical testing |