ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.4473_4495dup (p.Cys1499fs)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV004788231 SCV005398729 likely pathogenic Dilated cardiomyopathy 1G 2022-02-02 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with ARVC (MIM#607450) and other DSP-related cardiac disorders. (I) 0108 - This gene is associated with both recessive and dominant disease. Variants in this gene are usually inherited in a dominant manner, however rare reports of recessive inheritance have resulted in a more severe cardiac phenotype (OMIM). (I) 0115 - Variants in this gene are known to have variable expressivity. Age-dependent penetrance and variable expressivity are well-described aspects of arrhythmogenic cardiomyopathy (PMID: 29062697). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. At least ten other NMD-predicted variants have been reported as pathogenic or likely pathogenic in individuals with dilated cardiomyopathy (PMID: 27532257, ClinVar). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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.