Submissions for variant NM_001943.5(DSG2):c.3340C>T (p.Gln1114Ter)

dbSNP: rs776078563

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000642311	SCV000763980	uncertain significance	Arrhythmogenic right ventricular dysplasia 10	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1114*) in the DSG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 5 amino acid(s) of the DSG2 protein. 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: 534679). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
AiLife Diagnostics, AiLife Diagnostics	RCV002223236	SCV002501410	uncertain significance	not provided	2021-05-28	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV000642311	SCV004183359	pathogenic	Arrhythmogenic right ventricular dysplasia 10	2019-03-15	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1, PM2
Color Diagnostics, LLC DBA Color Health	RCV003532220	SCV004363243	uncertain significance	Cardiomyopathy	2023-02-01	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 15 of the DSG2 gene, creating a premature translation stop signal in the last coding exon. This variant is expected to escape nonsense-mediated decay and be expressed as a truncated protein. This variant has been reported in an individual affected with dilated cardiomyopathy and in two unaffected family members (PMID: 32826072). This variant has also been reported in a stillbirth case (PMID: 30615648), as well as in an individual with no documented incidence of cardiovascular disease (PMID: 33968641). This variant has not been identified 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.
All of Us Research Program, National Institutes of Health	RCV004003979	SCV004819992	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2024-03-05	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 15 of the DSG2 gene, creating a premature translation stop signal in the last coding exon. This variant is expected to escape nonsense-mediated decay and be expressed as a truncated protein. This variant has been reported in an individual affected with dilated cardiomyopathy and in two unaffected family members (PMID: 32826072). This variant has also been reported in a stillbirth case (PMID: 30615648), as well as in an individual with no documented incidence of cardiovascular disease (PMID: 33968641). This variant has not been identified 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.
GeneDx	RCV002223236	SCV005328058	uncertain significance	not provided	2024-02-02	criteria provided, single submitter	clinical testing	Reported in a stillborn male with normal karyotype and no reported malformations in published literature, although family history details and segregation studies were not described (PMID: 30615648); Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation as the last 5 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; This variant is associated with the following publications: (PMID: 30615648, 33968641)