Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000553791 | SCV000641301 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2022-08-09 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001524621 | SCV001734551 | uncertain significance | Cardiomyopathy | 2020-09-28 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 978 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 cardiovascular disorders in the literature. This variant has been identified in 1/251458 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV001524621 | SCV003838428 | uncertain significance | Cardiomyopathy | 2022-03-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003159824 | SCV003855693 | uncertain significance | Cardiovascular phenotype | 2022-11-27 | criteria provided, single submitter | clinical testing | The p.I978V variant (also known as c.2932A>G), located in coding exon 21 of the DSP gene, results from an A to G substitution at nucleotide position 2932. The isoleucine at codon 978 is replaced by valine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Center for Genomics, |
RCV003224326 | SCV003919900 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8; Lethal acantholytic epidermolysis bullosa; Woolly hair-skin fragility syndrome; Keratosis palmoplantaris striata 2; Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis | 2021-03-30 | criteria provided, single submitter | clinical testing | DSP NM_004415.3 exon 21 p.Ile978Val (c.2932A>G): This variant has not been reported in the literature and is present in 0.005% (1/18394) of East Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/6-7578066-A-G). This variant is present in ClinVar (Variation ID:465890). This amino acid is highly conserved among primates and mammals, but the variant amino acid Valine (Val) is present in several fish species. Additional computational prediction tools are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |