Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000766609 | SCV000576910 | uncertain significance | not provided | 2021-06-08 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26582918, 27535533) |
| Laboratory for Molecular Medicine, |
RCV000489524 | SCV000711605 | likely benign | not specified | 2017-03-07 | criteria provided, single submitter | clinical testing | p.Arg632Lys in exon 36 of TRDN: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, >30 mammal species have a lysine at this position. In addition, computation al prediction tools suggest it may not impact to the protein. It has also been i dentified in 0.2% (4/1926) of African chromosomes by the Exome Aggregation Conso rtium (ExAC, http://exac.broadinstitute.org; dbSNP rs181571822). |
| Ambry Genetics | RCV000620324 | SCV000738049 | likely benign | Cardiovascular phenotype | 2017-06-07 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Invitae | RCV002526020 | SCV000835534 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-07-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 632 of the TRDN protein (p.Arg632Lys). This variant is present in population databases (rs181571822, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with TRDN-related conditions. ClinVar contains an entry for this variant (Variation ID: 426462). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| ARUP Laboratories, |
RCV001286021 | SCV001472539 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 5 | 2019-12-27 | criteria provided, single submitter | clinical testing | The TRDN c.1895G>A, p.Arg632Lys variant (rs181571822), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 426462). This variant is found in the African population with an allele frequency of 0.1% (13/11,582 alleles) in the Genome Aggregation Database. The arginine at codon 632 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, given the lack of clinical and functional data, the significance of the p.Arg632Lys variant is uncertain at this time. Gene Statement: Pathogenic variants in TRDN are associated with autosomal recessive catecholaminergic polymorphic ventricular tachycardia 5, with or without muscle weakness (MIM: 615441). |