Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000805816 | SCV000945787 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2018-11-01 | criteria provided, single submitter | clinical testing | 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with DSP-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects codon 1028 of the DSP mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DSP protein. This variant also falls at the last nucleotide of exon 22 of the DSP coding sequence, which is part of the consensus splice site for this exon. |
| Ambry Genetics | RCV002325566 | SCV002608836 | uncertain significance | Cardiovascular phenotype | 2019-08-29 | criteria provided, single submitter | clinical testing | The c.3084G>A variant (also known as p.K1028K), located in coding exon 22 of the DSP gene, results from a G to A substitution at nucleotide position 3084. This nucleotide substitution does not change the at codon 1028. However, this change occurs in the last base pair of coding exon 22, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |