Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000235611 | SCV000294305 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-01-18 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003278718 | SCV004007799 | uncertain significance | Cardiovascular phenotype | 2023-03-19 | criteria provided, single submitter | clinical testing | The p.R1247Q variant (also known as c.3740G>A), located in coding exon 23 of the DSP gene, results from a G to A substitution at nucleotide position 3740. The arginine at codon 1247 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
| All of Us Research Program, |
RCV003998934 | SCV004826163 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma | 2023-05-30 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 1247 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 not been reported in individuals affected with DSP-related disorders in the literature. This variant has been identified in 2/250518 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. |