ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.3492C>G (p.Ile1164Met) (rs1561697488)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701028 SCV000829810 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-10-05 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 1164 of the DSP protein (p.Ile1164Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DSP-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Integrated Genetics/Laboratory Corporation of America RCV000780219 SCV000917310 uncertain significance not specified 2018-11-15 criteria provided, single submitter clinical testing Variant summary: DSP c.3492C>G (p.Ile1164Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 245390 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3492C>G in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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