Submissions for variant NM_001943.5(DSG2):c.1826dup (p.Leu610fs)

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

Total submissions: 5

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	RCV000709721	SCV000839949	likely pathogenic	Arrhythmogenic right ventricular dysplasia 10	2017-03-07	criteria provided, single submitter	clinical testing	The c.1826dup (p.Leu610Profs*50) variant has not been reported in public databases, nor has been observed in our patient cohort. This 1bp duplication in exon 12 results in a frameshift and the creation of a premature stop codon at amino acid position 660. This variant is thus expected to result in a loss of function of the protein. Frameshift variants and variants affecting the canonical splice sites have been reported in patients with cardiomyopathy, arrhythmogenic right ventricular. This variant is thus classified as likely pathogenic.
GeneDx	RCV001592914	SCV001825976	likely pathogenic	not provided	2020-03-25	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31447099)
Invitae	RCV000709721	SCV002231558	pathogenic	Arrhythmogenic right ventricular dysplasia 10	2023-09-24	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 585217). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu610Profs*50) 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).
Ambry Genetics	RCV002406655	SCV002715563	pathogenic	Cardiovascular phenotype	2022-06-02	criteria provided, single submitter	clinical testing	The c.1826dupG pathogenic mutation, located in coding exon 12 of the DSG2 gene, results from a duplication of G at nucleotide position 1826, causing a translational frameshift with a predicted alternate stop codon (p.L610Pfs*50). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Fulgent Genetics, Fulgent Genetics	RCV002507240	SCV002807635	likely pathogenic	Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB	2021-11-17	criteria provided, single submitter	clinical testing

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.