Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002524466 | SCV000961571 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 29 of the TRDN protein (p.Gly29Arg). This variant is present in population databases (rs763469367, gnomAD 0.05%). 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: 355228). 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: "Not Available"; 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. |
Gene |
RCV001571495 | SCV001795980 | uncertain significance | not provided | 2023-03-30 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function |
Ambry Genetics | RCV002446608 | SCV002679938 | uncertain significance | Cardiovascular phenotype | 2024-05-08 | criteria provided, single submitter | clinical testing | The c.85G>A (p.G29R) alteration is located in exon 2 (coding exon 2) of the TRDN gene. This alteration results from a G to A substitution at nucleotide position 85, causing the glycine (G) at amino acid position 29 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Victorian Clinical Genetics Services, |
RCV002470847 | SCV002768100 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 5 | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness (MIM#615441). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to arginine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (37 heterozygotes, 0 homozygotes). Additionally, an alternative nucleotide change, resulting in the same amino acid change, is present in the gnomAD population database (v2) at <0.01 (2 heterozygotes, 0 homozygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. The variant has previously been reported once as a VUS (ClinVar). (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
Fulgent Genetics, |
RCV002504171 | SCV002814170 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1; Catecholaminergic polymorphic ventricular tachycardia 5 | 2021-11-01 | criteria provided, single submitter | clinical testing |