ClinVar Miner

Submissions for variant NM_024334.2(TMEM43):c.797G>A (p.Arg266Gln) (rs193922707)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000030554 SCV000441302 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000030554 SCV000053225 uncertain Arrhythmogenic right ventricular cardiomyopathy 2011-08-18 criteria provided, single submitter curation Converted during submission to Uncertain significance.
Invitae RCV000642420 SCV000764098 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 5 2017-11-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 266 of the TMEM43 protein (p.Arg266Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs193922707, ExAC 0.06%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with TMEM43-related disease. ClinVar contains an entry for this variant (Variation ID: 36872). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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