ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.3061_3062del (p.Ser1021fs)

dbSNP: rs397516706
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000642319 SCV000763988 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2022-06-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1021Leufs*16) in the DSG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 98 amino acid(s) of the DSG2 protein. This variant is present in population databases (rs397516706, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with clinical features of arrhythmogenic right ventricular cardiomyopathy (PMID: 23810883, 23812740). ClinVar contains an entry for this variant (Variation ID: 44310). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the DSG2 protein in which other variant(s) (p.Gly1083Ser) have been observed in individuals with DSG2-related conditions (PMID: 21636032). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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 RCV002444478 SCV002753816 uncertain significance Cardiovascular phenotype 2023-12-26 criteria provided, single submitter clinical testing The c.3061_3062delAG variant, located in coding exon 15 of the DSG2 gene, results from a deletion of two nucleotides at nucleotide positions 3061 to 3062, causing a translational frameshift with a predicted alternate stop codon (p.S1021Lfs*16). This alteration occurs at the 3' terminus of theDSG2 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 8% of the protein. The exact functional effect of this alteration is unknown. This variant has been reported in arrhythmogenic right ventricular cardiomyopathy (ARVC) cohorts; however, clinical details were limited, and at least one case had an additional cardiac variant detected (Baskin B et al. Hum. Genet., 2013 Nov;132:1245-52; Perrin MJ et al. J. Am. Coll. Cardiol., 2013 Nov;62:1772-9; Adler A et al. Circ Arrhythm Electrophysiol, 2016 Jan;9:e003440). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002477090 SCV002780350 uncertain significance Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB 2021-11-17 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037297 SCV000060954 likely pathogenic Arrhythmogenic right ventricular cardiomyopathy 2009-08-06 no assertion criteria provided clinical testing

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