ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.3281_3283delinsTTA (p.Gly1094_His1095delinsValAsn)

dbSNP: rs386802145
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156648 SCV000206369 uncertain significance not specified 2014-07-10 criteria provided, single submitter clinical testing The Gly1094_His1095delinsValAsn variant in DSG2 has not been previously reported in individuals with cardiomyopathy. This variant is equivalent to 2 missense va riants (Gly1094Val and His1095Asn), though because they occur on the same copy o f the gene (in cis), they are described as above. Each missense variant has been identified in 3/3969 African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs144313973 and rs140193292), though it is assumed that these actually represent this variant (dbSNP rs386802 145). This variant is a deletion of 2 amino acids at position 1094 and 1095 and an insertion of two different amino acids at these positions and is not predicte d to alter the protein reading-frame. While the affected amino acids are not wel l conserved, it is unclear if this variant will impact the protein. In summary, the clinical significance of the Gly1094_His1095delinsValAsn variant is uncertai n.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000156648 SCV000697888 uncertain significance not specified 2022-03-08 criteria provided, single submitter clinical testing Variant summary: DSG2 c.3281_3283delinsTTA (p.Gly1094_His1095delinsValAsn) results in an in-frame deletion-insertion that is predicted to delete two amino acids and also cause insert in two amino acids in the last exon of the protein. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 280622 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3281_3283delinsTTA in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Color Diagnostics, LLC DBA Color Health RCV001179113 SCV001343713 likely benign Cardiomyopathy 2022-05-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV002444646 SCV002611524 likely benign Cardiovascular phenotype 2022-03-31 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV002484954 SCV002780086 uncertain significance Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB 2022-05-02 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001179113 SCV004240510 likely benign Cardiomyopathy 2023-02-15 criteria provided, single submitter clinical testing

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