Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000641793 | SCV000763442 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2024-01-03 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV001183054 | SCV001348709 | uncertain significance | Cardiomyopathy | 2022-12-12 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glutamic acid at codon 1258 of the DSP protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two individuals suspected of having arrhythmogenic right ventricular cardiomyopathy (PMID: 24070718). This variant has been identified in 4/250766 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. |
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV001256842 | SCV001433327 | uncertain significance | Arrhythmogenic right ventricular dysplasia 1 | 2020-04-19 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV001811134 | SCV002049571 | uncertain significance | not provided | 2020-10-01 | criteria provided, single submitter | clinical testing | The DSP c.3774C>A; p.Asp1258Glu variant (rs748733750) is reported in the literature in several individuals affected with arrhythmogenic right ventricular cardiomyopathy, although its clinical significance was not determined (Bauce 2011, Rigato 2013). This variant is found on only four chromosomes (4/250766 alleles) in the Genome Aggregation Database. The aspartate at codon 1258 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, due to limited information, the clinical significance of the p.Asp1258Glu variant is uncertain at this time. References: Bauce et al. Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations. Heart Rhythm. 2011 Nov;8(11):1686-95. Rigato I et al. Compound and digenic heterozygosity predicts lifetime arrhythmic outcome and sudden cardiac death in desmosomal gene-related arrhythmogenic right ventricular cardiomyopathy. Circ Cardiovasc Genet. 2013 Dec;6(6):533-42. |
| Ambry Genetics | RCV002343279 | SCV002620762 | uncertain significance | Cardiovascular phenotype | 2021-02-17 | criteria provided, single submitter | clinical testing | The p.D1258E variant (also known as c.3774C>A), located in coding exon 23 of the DSP gene, results from a C to A substitution at nucleotide position 3774. The aspartic acid at codon 1258 is replaced by glutamic acid, an amino acid with highly similar properties. This variant has been reported in overlapping arrhythmogenic right ventricular cardiomyopathy (ARVC) cohorts with limited clinical details provided (Bauce B et al. Heart Rhythm, 2011 Nov;8:1686-95; Rigato I et al. Circ Cardiovasc Genet, 2013 Dec;6:533-42; Zorzi A et al. Europace, 2016 Jul;18:1086-94). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |