Submissions for variant NM_001943.5(DSG2):c.307_308del (p.Val103fs)

Minimum review status:		Collection method:
Minimum conflict level: Report conflict between different conditions
		ClinVar version:

Total submissions: 2

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520634	SCV000619766	likely pathogenic	not provided	2017-08-03	criteria provided, single submitter	clinical testing	Although the c.307_308delGT likely pathogenic variant in the DSG2 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon valine 103, changing it to a leucine, and creating a premature stop codon at position 2 of the new reading frame, denoted p.Val103LeufsX2. This likely pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the DSG2 gene have been reported in Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. The c.307_308delGT variant has not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). However, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003631130	SCV004524823	pathogenic	Arrhythmogenic right ventricular dysplasia 10	2024-01-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val103Leufs*2) in the DSG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSG2 are known to be pathogenic (PMID: 17105751, 31386562). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 451114). For these reasons, this variant has been classified as Pathogenic.

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.