Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000156291 | SCV000206009 | uncertain significance | not specified | 2014-01-28 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Gln876Glu varia nt in DSC2 has not been reported in individuals with cardiomyopathy or in large population studies. Glutamine (Gln) at position 2626 is not conserved in evoluti on, and several fish species have the variant amino acid (glutamate,Glu) at this position, suggesting that this change may be tolerated. Additional computationa l analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) d o not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the clinical significance of the Gln876Gl u variant. |
Invitae | RCV001302850 | SCV001492074 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2022-07-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 876 of the DSC2 protein (p.Gln876Glu). This variant is present in population databases (rs727504906, gnomAD 0.007%). 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: 179501). 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. |
Color Diagnostics, |
RCV003531986 | SCV004363058 | uncertain significance | Cardiomyopathy | 2022-11-06 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with glutamic acid at codon 876 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 DSC2-related disorders in the literature. This variant has been identified in 1/31386 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. |
All of Us Research Program, |
RCV003998307 | SCV004831733 | uncertain significance | Familial isolated arrhythmogenic right ventricular dysplasia | 2023-07-10 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with glutamic acid at codon 876 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 DSC2-related disorders in the literature. This variant has been identified in 1/31386 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 | RCV004019876 | SCV005028720 | uncertain significance | Cardiovascular phenotype | 2024-01-22 | criteria provided, single submitter | clinical testing | The p.Q876E variant (also known as c.2626C>G), located in coding exon 16 of the DSC2 gene, results from a C to G substitution at nucleotide position 2626. The glutamine at codon 876 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |