ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.408A>G (p.Arg136=) (rs561653481)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000250186 SCV000319151 uncertain significance Cardiovascular phenotype 2015-09-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Synonymous alterations with insufficient evidence to classify as benign
Color RCV000771973 SCV000904927 uncertain significance Cardiomyopathy 2018-10-02 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This is a synonymous variant that does not change the amino acid sequence of the DSC2 protein. However, computational splicing tools suggest that this variant may 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 10/246062 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Invitae RCV000533412 SCV000645017 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 11 2018-04-25 criteria provided, single submitter clinical testing This sequence change affects codon 136 of the DSC2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DSC2 protein. This variant is present in population databases (rs561653481, ExAC 0.05%) but has not been reported in the literature in individuals with a DSC2-related disease. ClinVar contains an entry for this variant (Variation ID: 234987). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare silent change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000223837 SCV000280079 uncertain significance not specified 2014-05-16 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. This variant is located in exon 4 (of 16 exons) does not change the amino acid at codon 136, however BDGP and ESEfinder splice prediction tools predict this alteration to create an alternate donor splice site. There is no direct function evidence available. The arginine at codon 136 is conserved across species, as are neighboring amino acids. In total the variant has not been seen in ~6,500 individuals from publicly available population datasets. There is no variation at codon 136 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6,500 Caucasian and African American individuals (as of 11/22/13). Note that this dataset does not match the patient's ancestry (Asian). There is also no variation at this codon listed in dbSNP or 1000 genomes (as of 11/22/13).

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