ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.6451C>T (p.Arg2151Trp)

gnomAD frequency: 0.00002  dbSNP: rs181608152
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000641783 SCV000763432 benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2025-02-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001524939 SCV001734920 uncertain significance Cardiomyopathy 2022-08-29 criteria provided, single submitter clinical testing This missense variant replaces arginine with tryptophan at codon 2151 of the DSP protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 17/282560 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.
GeneDx RCV001766380 SCV001991439 uncertain significance not provided 2019-07-31 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
All of Us Research Program, National Institutes of Health RCV004003927 SCV004814264 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2024-08-13 criteria provided, single submitter clinical testing This missense variant replaces arginine with tryptophan at codon 2151 of the DSP protein. Computational prediction tools indicate that this variant has a deleterious impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual affected with cardiomyopathy (PMID: 37477868). This variant has been identified in 17/282560 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 RCV004992432 SCV005575868 uncertain significance Cardiovascular phenotype 2024-10-10 criteria provided, single submitter clinical testing The p.R2151W variant (also known as c.6451C>T), located in coding exon 24 of the DSP gene, results from a C to T substitution at nucleotide position 6451. The arginine at codon 2151 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on data from gnomAD, the frequency for this variant is above the maximum credible frequency for a disease-causing variant in this gene based on internally established thresholds (Karczewski et al. Nature. 2020 May;581(7809):434-443; Whiffin et al. Genet Med. 2017 10;19:1151-1158). Based on the available evidence, the clinical significance of this variant remains unclear.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001766380 SCV005879826 uncertain significance not provided 2024-11-12 criteria provided, single submitter clinical testing The DSP c.6451C>T; p.Arg2151Trp variant (rs181608152, ClinVar Variation ID: 534285) is reported in the literature in one individual affected with cardiomyopathy (Akinrinade 2023). This variant is found primarily in the South Asian population with an allele frequency of 0.05% (15/30612 alleles, including 1 homozygote) in the Genome Aggregation Database (v2.1.1). Computational analyses predict that this variant is deleterious (REVEL: 0.837). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Akinrinade O et al. Age and Sex Differences in the Genetics of Cardiomyopathy. J Cardiovasc Transl Res. 2023 Dec;16(6):1287-1302. PMID: 37477868.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV004992432 SCV005882803 uncertain significance Cardiovascular phenotype 2025-02-17 criteria provided, single submitter clinical testing

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