ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.4514C>T (p.Ala1505Val)

gnomAD frequency: 0.00002  dbSNP: rs375919492
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000218906 SCV000271728 uncertain significance not specified 2015-08-12 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ala1505Val va riant in DSP has not been previously reported in individuals with cardiomyopathy , but has been identified in 6/65984 European chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs375919492). Alanine (Ala) at position 1505 is not conserved in evolution and 2 mammals and 1 amphib ian (squirrel, Wedell seal, and X. tropicalis) carry a valine (Val), raising the possibility that this change may be tolerated. Although this suggests that the variant may not impact the protein, this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Al a1505Val variant is uncertain, these data suggest that it is more likely to be b enign.
Invitae RCV000641799 SCV000763449 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2024-01-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001187399 SCV001354201 uncertain significance Cardiomyopathy 2023-12-06 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 1505 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 arrhythmogenic right ventricular cardiomyopathy (PMID: 20857253). This variant has been identified in 19/280894 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 RCV002338679 SCV002640141 uncertain significance Cardiovascular phenotype 2022-02-04 criteria provided, single submitter clinical testing The p.A1505V variant (also known as c.4514C>T), located in coding exon 23 of the DSP gene, results from a C to T substitution at nucleotide position 4514. The alanine at codon 1505 is replaced by valine, an amino acid with similar properties. This variant has been detected in a cohort of cases with confirmed or suspected arrhythmogenic right ventricular cardiomyopathy; however, details were limited (Tan BY et al. J Cardiovasc Transl Res, 2010 Dec;3:663-73). 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.

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.