ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.464_465insT (p.Glu156fs)

dbSNP: rs794728091
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181238 SCV000233517 pathogenic not provided 2022-07-09 criteria provided, single submitter clinical testing Reported in at least one individual in association with ARVC in published literature (Bhonsale et al., 2015) and other individuals referred for ARVC genetic testing at GeneDx; 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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25616645, 31589614, 26582918, 31386562)
Invitae RCV000799959 SCV000939651 pathogenic Arrhythmogenic right ventricular dysplasia 10 2023-08-28 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: 199822). This premature translational stop signal has been observed in individual(s) with arrythmogenic right ventricular cardiomyopathy (PMID: 25616645, 31386562). This variant is present in population databases (rs794728091, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Glu156Argfs*14) 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 RCV002336442 SCV002639892 pathogenic Cardiovascular phenotype 2019-05-17 criteria provided, single submitter clinical testing The c.464_465insT pathogenic mutation, located in coding exon 5 of the DSG2 gene, results from an insertion of one nucleotide at position 464, causing a translational frameshift with a predicted alternate stop codon (p.E156Rfs*14). This mutation was identified in 1 individual from an arrhythmogenic right ventricular cardiomyopathy registry (Bhonsale A et al. Eur. Heart J., 2015 Apr;36:847-55). In addition to the clinical data presented in the literature, 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.

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