ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.1970C>T (p.Thr657Ile)

dbSNP: rs1014373689
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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 RCV001176944 SCV001341047 uncertain significance Cardiomyopathy 2023-03-23 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 657 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 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.
Invitae RCV001875831 SCV002204611 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-05-22 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 919020). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. This variant has not been reported in the literature in individuals affected with DSP-related conditions. This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 657 of the DSP protein (p.Thr657Ile). This variant is not present in population databases (gnomAD no frequency).
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001176944 SCV003838422 uncertain significance Cardiomyopathy 2023-06-07 criteria provided, single submitter clinical testing

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