ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.3023C>T (p.Thr1008Ile)

dbSNP: rs1334187363
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000774043 SCV000907743 uncertain significance Cardiomyopathy 2019-12-02 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 1008 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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 RCV002440604 SCV002753870 uncertain significance Cardiovascular phenotype 2021-02-04 criteria provided, single submitter clinical testing The p.T1008I variant (also known as c.3023C>T), located in coding exon 22 of the DSP gene, results from a C to T substitution at nucleotide position 3023. The threonine at codon 1008 is replaced by isoleucine, an amino acid with similar 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003768358 SCV004573673 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-08-11 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: 629341). This variant has not been reported in the literature in individuals affected with DSP-related conditions. 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 1008 of the DSP protein (p.Thr1008Ile).

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