Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001369644 | SCV001566088 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2023-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 833 of the DSG2 protein (p.Phe833Cys). This variant is not present in population databases (gnomAD no frequency). 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: 1060244). 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. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003994284 | SCV004813888 | uncertain significance | not specified | 2024-02-27 | criteria provided, single submitter | clinical testing | Variant summary: DSG2 c.2498T>G (p.Phe833Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249274 control chromosomes. 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.2498T>G in individuals affected with cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1060244). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Ambry Genetics | RCV004995721 | SCV005575796 | uncertain significance | Cardiovascular phenotype | 2024-10-03 | criteria provided, single submitter | clinical testing | The c.2498T>G (p.F833C) alteration is located in exon 15 (coding exon 15) of the DSG2 gene. This alteration results from a T to G substitution at nucleotide position 2498, causing the phenylalanine (F) at amino acid position 833 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |