ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.8390T>C (p.Ile2797Thr)

gnomAD frequency: 0.00001  dbSNP: rs769734918
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000809341 SCV000949490 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2024-10-27 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001182978 SCV001348617 uncertain significance Cardiomyopathy 2023-10-11 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 2797 of the DSP 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 been reported in one individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 27532257). This variant has been identified in 8/282736 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 RCV002440739 SCV002677912 uncertain significance Cardiovascular phenotype 2023-08-23 criteria provided, single submitter clinical testing The p.I2797T variant (also known as c.8390T>C), located in coding exon 24 of the DSP gene, results from a T to C substitution at nucleotide position 8390. The isoleucine at codon 2797 is replaced by threonine, an amino acid with similar properties. This variant has been reported in an arrhythmogenic right ventricular cardiomyopathy (ARVC) cohort; however, clinical details were limited (Walsh R et al. Genet. Med. 2017;19:192-203). This amino acid position is not 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.
PreventionGenetics, part of Exact Sciences RCV003413625 SCV004109345 uncertain significance DSP-related disorder 2022-09-27 criteria provided, single submitter clinical testing The DSP c.8390T>C variant is predicted to result in the amino acid substitution p.Ile2797Thr. This variant was reported in an individual with arrhythmogenic right ventricular cardiomyopathy (Table S1A - Walsh et al. 2017. PubMed ID: 27532257). This variant is reported in 0.010% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-7585885-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
GeneDx RCV005250117 SCV005900858 uncertain significance not provided 2024-09-24 criteria provided, single submitter clinical testing Identified in a patient with ARVC in published literature (PMID: 27532257); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31402444, 27532257)

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