ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.652A>G (p.Ile218Val)

dbSNP: rs987363401
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481934 SCV000571751 uncertain significance not provided 2017-04-10 criteria provided, single submitter clinical testing The I218V variant of uncertain significance in the DSP gene has not been published as a pathogenic or benign variantto our knowledge. This variant was not observed in approximately 6,500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in thesepopulations. The I218V variant is a conservative amino acid substitution, which is not likely to impact secondaryprotein structure as these residues share similar properties. Furthermore, this substitution occurs at a position whereamino acids with similar properties to Isoleucine are tolerated across species, and V218 is tolerated in at least onespecies. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the proteinstructure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Color Diagnostics, LLC DBA Color Health RCV001177924 SCV001342237 uncertain significance Cardiomyopathy 2023-03-16 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 218 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). 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 been identified in 1/251446 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.

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