ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.7552G>A (p.Val2518Ile)

gnomAD frequency: 0.00008  dbSNP: rs757394666
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000236392 SCV000294315 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-11-03 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001181789 SCV001347015 uncertain significance Cardiomyopathy 2023-03-09 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 2518 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 with ventricular fibrillation and an individual with arrhythmia (PMID: 29032884, Color internal data). This variant has been identified in 9/282880 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.
Ambry Genetics RCV002392736 SCV002675193 uncertain significance Cardiovascular phenotype 2021-05-28 criteria provided, single submitter clinical testing The p.V2518I variant (also known as c.7552G>A), located in coding exon 24 of the DSP gene, results from a G to A substitution at nucleotide position 7552. The valine at codon 2518 is replaced by isoleucine, an amino acid with highly similar properties. This alteration has been reported in an idiopathic ventricular fibrillation cohort (Leinonen JT et al. Int J Cardiol, 2018 Jan;250:139-145). This amino acid position is 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.
Revvity Omics, Revvity RCV003144172 SCV003829137 uncertain significance not provided 2022-06-03 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003977702 SCV004790103 uncertain significance DSP-related condition 2023-12-13 criteria provided, single submitter clinical testing The DSP c.7552G>A variant is predicted to result in the amino acid substitution p.Val2518Ile. This variant has been reported in an individual with idiopathic ventricular fibrillation and in another individual with hypertrophic cardiomyopathy, although additional variants were identified in cardiac-related genes in these individuals (Patient I34, Leinonen et al. 2018. PubMed ID: 29032884; Carlo et al. 2022. PubMed ID: 35475074). This variant is reported in 0.011% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.