Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001233157 | SCV001405739 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-03-26 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002447170 | SCV002679812 | uncertain significance | Cardiovascular phenotype | 2020-12-09 | criteria provided, single submitter | clinical testing | The p.R2801H variant (also known as c.8402G>A), located in coding exon 24 of the DSP gene, results from a G to A substitution at nucleotide position 8402. The arginine at codon 2801 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported in a sudden unexplained death cohort (Sanchez O et al. PLoS One, 2016 Dec;11:e0167358). This amino acid position is not well conserved in available vertebrate species. 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. |
Color Diagnostics, |
RCV003532912 | SCV004363538 | uncertain significance | Cardiomyopathy | 2022-03-08 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with histidine at codon 2801 of the DSP 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 been reported in an individual affected with sudden explained death (PMID: 27930701). This variant has been identified in 5/251216 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. |