ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2768C>G (p.Pro923Arg)

gnomAD frequency: 0.00001  dbSNP: rs1408093009
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV001256689 SCV001433087 uncertain significance Dilated cardiomyopathy 1A 2020-02-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001301692 SCV001490870 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-10-29 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 923 of the DSG2 protein (p.Pro923Arg). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 978279). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DSG2 protein function with a negative predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV002491864 SCV002781240 uncertain significance Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB 2022-04-22 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV003532922 SCV004363227 uncertain significance Cardiomyopathy 2023-10-25 criteria provided, single submitter clinical testing This missense variant replaces proline with arginine at codon 923 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 cardiovascular disorders in the literature. This variant has been identified in 1/249156 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.
All of Us Research Program, National Institutes of Health RCV004004923 SCV004821838 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-11-20 criteria provided, single submitter clinical testing This missense variant replaces proline with arginine at codon 923 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 cardiovascular disorders in the literature. This variant has been identified in 1/249156 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.
Ambry Genetics RCV004619595 SCV005117155 uncertain significance Cardiovascular phenotype 2024-05-29 criteria provided, single submitter clinical testing The c.2768C>G (p.P923R) alteration is located in exon 15 (coding exon 15) of the DSG2 gene. This alteration results from a C to G substitution at nucleotide position 2768, causing the proline (P) at amino acid position 923 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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