ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1784A>G (p.His595Arg)

gnomAD frequency: 0.00001  dbSNP: rs371326860
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002019523 SCV002283222 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2022-06-18 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 595 of the DSG2 protein (p.His595Arg). This variant is present in population databases (rs371326860, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV003375539 SCV004096019 uncertain significance Cardiovascular phenotype 2024-10-09 criteria provided, single submitter clinical testing The c.1784A>G (p.H595R) alteration is located in exon 12 (coding exon 12) of the DSG2 gene. This alteration results from a A to G substitution at nucleotide position 1784, causing the histidine (H) at amino acid position 595 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004011098 SCV004827071 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2024-01-11 criteria provided, single submitter clinical testing This missense variant replaces histidine with arginine at codon 595 of the DSG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with DSG2-related disorders in the literature. This variant has been identified in 3/280564 chromosomes 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.

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