Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002537245 | SCV000947252 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-03-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 266 of the TRDN protein (p.Gln266Arg). This variant is present in population databases (rs200068375, gnomAD 0.2%). 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: 651783). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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. |
| Ambry Genetics | RCV002406801 | SCV002675775 | likely benign | Cardiovascular phenotype | 2022-06-06 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
| Center for Genomics, |
RCV003224476 | SCV003920593 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 5 | 2021-03-30 | criteria provided, single submitter | clinical testing | TRDN NM_006073.3 exon 9 p.Gln266Arg (c.797A>G): This variant has not been reported in the literature and is present in 0.1% (31/19358) of Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/6-123818394-T-C). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. Of note, splice prediction tools suggest that this variant may affect splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |