ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1555G>T (p.Asp519Tyr)

gnomAD frequency: 0.00003  dbSNP: rs778119035
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181221 SCV000233500 uncertain significance not provided 2021-09-09 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 199809; Landrum et al., 2016)
Labcorp Genetics (formerly Invitae), Labcorp RCV000803625 SCV000943505 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2022-03-09 criteria provided, single submitter clinical testing 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 199809). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is present in population databases (rs778119035, gnomAD 0.01%). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 519 of the DSG2 protein (p.Asp519Tyr).
AiLife Diagnostics, AiLife Diagnostics RCV000181221 SCV002501775 uncertain significance not provided 2021-07-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV002399643 SCV002704370 uncertain significance Cardiovascular phenotype 2024-08-01 criteria provided, single submitter clinical testing The c.1555G>T (p.D519Y) alteration is located in exon 11 (coding exon 11) of the DSG2 gene. This alteration results from a G to T substitution at nucleotide position 1555, causing the aspartic acid (D) at amino acid position 519 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002478605 SCV002775413 uncertain significance Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB 2021-08-20 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003996617 SCV004825571 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2024-08-06 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with tyrosine at codon 519 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 3/280850 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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