ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.3144_3147del (p.Arg1049fs)

dbSNP: rs758822081
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482922 SCV000569072 uncertain significance not provided 2024-04-18 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation as the last 70 amino acids are replaced with 1 different amino acid, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001212540 SCV001384127 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-08-03 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 420292). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is present in population databases (rs758822081, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Arg1049Phefs*2) in the DSG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 70 amino acid(s) of the DSG2 protein. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Ambry Genetics RCV002323825 SCV002609044 uncertain significance Cardiovascular phenotype 2024-02-26 criteria provided, single submitter clinical testing The c.3144_3147delAAGA variant, located in coding exon 15 of the DSG2 gene, results from a deletion of 4 nucleotides at nucleotide positions 3144 to 3147, causing a translational frameshift with a predicted alternate stop codon (p.R1049Ffs*2). This alteration has been reported in association with dilated cardiomyopathy (DCM) (Yang Q et al. J Am Heart Assoc, 2022 Oct;11:e025257). This alteration occurs at the 3' terminus of theDSG2 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 70 amino acids of the protein. The exact functional effect of this alteration is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002475933 SCV002783922 uncertain significance Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB 2021-08-09 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000482922 SCV004224477 uncertain significance not provided 2022-06-14 criteria provided, single submitter clinical testing PVS1_moderate

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