ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.3646A>G (p.Ile1216Val) (rs199795359)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000247902 SCV000320258 likely benign Cardiovascular phenotype 2018-04-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Subpopulation frequency in support of benign classification
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171915 SCV000055167 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
GeneDx RCV000038029 SCV000233606 uncertain significance not specified 2013-03-08 criteria provided, single submitter clinical testing p.Ile1216Val (ATT>GTT): c.3646 A>G in exon 23 of the DSP gene (NM_004415.2). The Ile1216Val variant in the DSP gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Although Ile1216Val results in a conservative amino acid substitution of one non-polar amino acid for another, this substitution occurs at a position that is conserved across species. The Ile1216Val variant was not observed in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, Ile1216Val was observed in 0.4% of Asian alleles in the 1000 Genomes database. In silico algorithms are not consistent in their predictions but at least two concur that Ile1216Val is benign to the protein structure/function. In addition, mutations in nearby residues have not been reported (van der Zwaag P et al., 2009) indicating this region of the protein may tolerate change. With the clinical and molecular information available at this time, we cannot definitively determine if Ile1216Val is a disease-causing mutation or a rare benign variant. The variant is found in ARVC panel(s).
Invitae RCV000466878 SCV000555777 likely benign Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2016-09-20 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038029 SCV000061695 uncertain significance not specified 2008-03-01 no assertion criteria provided clinical testing

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