ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.355C>T (p.Arg119Ter)

gnomAD frequency: 0.00001  dbSNP: rs753052874
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001524075 SCV001733837 uncertain significance Cardiomyopathy 2020-11-03 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 4 of the DSG2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual from a cohort of participants in a rare disease genome sequencing study who were not known to have an inherited cardiac condition (PMID: 32686758). This variant has been identified in 3/248512 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion for a pathogenic role, clinical relevance of loss-of-function DSC2 truncation and splice variants in autosomal dominant arrhythmogenic cardiomyopathy is not yet clearly established. 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 RCV002334573 SCV002618896 pathogenic Cardiovascular phenotype 2018-12-19 criteria provided, single submitter clinical testing The p.R119* pathogenic mutation (also known as c.355C>T), located in coding exon 4 of the DSG2 gene, results from a C to T substitution at nucleotide position 355. This changes the amino acid from an arginine to a stop codon within coding exon 4. 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.
GeneDx RCV002466679 SCV002762655 pathogenic not provided 2022-11-29 criteria provided, single submitter clinical testing Nonsense 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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33949662, 31638835, 34500006, 32686758, 33087929, 32877757)
Invitae RCV003771576 SCV004696987 pathogenic Arrhythmogenic right ventricular dysplasia 10 2024-01-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg119*) 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 present in population databases (rs753052874, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with DSG2-related conditions (PMID: 34500006). ClinVar contains an entry for this variant (Variation ID: 1171153). For these reasons, this variant has been classified as Pathogenic.
All of Us Research Program, National Institutes of Health RCV004007253 SCV004819435 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-05-31 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 4 of the DSG2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual from a cohort of participants in a rare disease genome sequencing study who were not known to have an inherited cardiac condition (PMID: 32686758). This variant has been identified in 3/248512 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion for a pathogenic role, clinical relevance of loss-of-function DSG2 truncation and splice variants in autosomal dominant arrhythmogenic cardiomyopathy is not yet clearly established. 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.
OMIM RCV002251768 SCV002520419 pathogenic Dilated cardiomyopathy 1BB 2022-04-22 no assertion criteria provided literature only

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