ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.721G>A (p.Ala241Thr)

gnomAD frequency: 0.00003  dbSNP: rs371918777
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
AiLife Diagnostics, AiLife Diagnostics RCV002223428 SCV002501774 uncertain significance not provided 2021-07-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV002373049 SCV002668757 uncertain significance Cardiovascular phenotype 2024-09-30 criteria provided, single submitter clinical testing The p.A241T variant (also known as c.721G>A), located in coding exon 7 of the DSG2 gene, results from a G to A substitution at nucleotide position 721. The alanine at codon 241 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002481031 SCV002783307 uncertain significance Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB 2021-09-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003089161 SCV003479764 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-03-26 criteria provided, single submitter clinical testing This variant is present in population databases (rs371918777, gnomAD 0.01%). 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DSG2 protein function. ClinVar contains an entry for this variant (Variation ID: 1677394). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 241 of the DSG2 protein (p.Ala241Thr).
All of Us Research Program, National Institutes of Health RCV004005532 SCV004834278 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2024-08-06 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 241 of the DSG2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 2/248992 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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