ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.4573A>G (p.Ile1525Val) (rs145796901)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038053 SCV000061719 uncertain significance not specified 2012-06-06 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Ile1525Val vari ant in DSP has not been reported in the literature nor previously identified by our laboratory. This variant has been identified in 1/7020 European American chr omosomes from a broad population by the NHLBI Exome Sequencing Project (http://e vs.gs.washington.edu/EVS/; dbSNP rs145796901), though this could represent a pre symptomatic individual in the general population. Computational analyses (bioche mical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) sugge st that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. Additional information is needed to fully assess the clinical significance of this variant.
Invitae RCV000464870 SCV000543262 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2016-12-15 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 1525 of the DSP protein (p.Ile1525Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs145796901, ExAC 0.003%) but has not been reported in the literature in individuals with a DSP-related disease. ClinVar contains an entry for this variant (Variation ID: 44918). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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