ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.3353C>T (p.Ser1118Phe)

gnomAD frequency: 0.00014  dbSNP: rs368703304
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479999 SCV000564949 uncertain significance not provided 2022-09-16 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV000537280 SCV000641984 likely benign Arrhythmogenic right ventricular dysplasia 10 2024-01-16 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001177921 SCV001342234 uncertain significance Cardiomyopathy 2023-02-22 criteria provided, single submitter clinical testing This missense variant replaces serine with phenylalanine at codon 1118 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 DSG2-related disorders in the literature. This variant has been identified in 15/280430 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 RCV002323815 SCV002607145 likely benign Cardiovascular phenotype 2021-07-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
All of Us Research Program, National Institutes of Health RCV004002240 SCV004819994 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-10-02 criteria provided, single submitter clinical testing This missense variant replaces serine with phenylalanine at codon 1118 of the DSG2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 15/280430 chromosomes (14/24144 African chromosomes) in the general population by the Genome Aggregation Database (gnomAD). 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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