Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000695803 | SCV000824324 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2023-06-17 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with DSC2-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 573988). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 566 of the DSC2 protein (p.Ile566Thr). |
Ambry Genetics | RCV002532330 | SCV003615076 | uncertain significance | Inborn genetic diseases | 2022-02-10 | criteria provided, single submitter | clinical testing | The c.1697T>C (p.I566T) alteration is located in exon 12 (coding exon 12) of the DSC2 gene. This alteration results from a T to C substitution at nucleotide position 1697, causing the isoleucine (I) at amino acid position 566 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV003532241 | SCV004363085 | uncertain significance | Cardiomyopathy | 2021-06-28 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with threonine at codon 566 of the DSC2 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/250832 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. |