ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.6587C>T (p.Thr2196Ile)

gnomAD frequency: 0.00001  dbSNP: rs958098310
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000698214 SCV000826864 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-04-07 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 575874). This missense change has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 29606362). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2196 of the DSP protein (p.Thr2196Ile).
Ambry Genetics RCV002360781 SCV002664670 uncertain significance Cardiovascular phenotype 2020-12-01 criteria provided, single submitter clinical testing The p.T2196I variant (also known as c.6587C>T), located in coding exon 24 of the DSP gene, results from a C to T substitution at nucleotide position 6587. The threonine at codon 2196 is replaced by isoleucine, an amino acid with similar properties. This variant was reported in one individual from an arrhythmogenic right ventricular cardiomyopathy (ARVC) cohort (Ruiz Salas A et al. Rev Esp Cardiol (Engl Ed), 2018 Dec;71:1018-1026). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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