Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001126682 | SCV001285909 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Color Diagnostics, |
RCV001176570 | SCV001340593 | uncertain significance | Cardiomyopathy | 2023-08-02 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with leucine at codon 5 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 1/120154 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. |
Ambry Genetics | RCV002393362 | SCV002700551 | uncertain significance | Cardiovascular phenotype | 2022-08-14 | criteria provided, single submitter | clinical testing | The p.R5L variant (also known as c.14G>T), located in coding exon 1 of the DSC2 gene, results from a G to T substitution at nucleotide position 14. The arginine at codon 5 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV001126682 | SCV002815775 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2022-02-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001126682 | SCV003456864 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2022-03-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 5 of the DSC2 protein (p.Arg5Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with DSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 891405). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
All of Us Research Program, |
RCV004000252 | SCV004819396 | uncertain significance | Familial isolated arrhythmogenic right ventricular dysplasia | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with leucine at codon 5 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 1/120154 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. |
Clinical Genomics Laboratory, |
RCV001126682 | SCV005045530 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2021-07-21 | criteria provided, single submitter | clinical testing | The p.Arg5Leu variant in the DSC2gene has not been previously reported in association with disease. This variant has been identified in 1/21,118 South Asian chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Computational tools predict that this variant does not impact protein function; however, the accuracy of in silicoalgorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Arg5Leu variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PM2; BP4] |