ClinVar Miner

Submissions for variant NM_024334.3(TMEM43):c.1021C>T (p.Arg341Ter) (rs778127887)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000201506 SCV000256202 likely pathogenic Cardiomyopathy criteria provided, single submitter clinical testing
Color Health, Inc RCV000201506 SCV001350782 uncertain significance Cardiomyopathy 2019-08-21 criteria provided, single submitter clinical testing
Invitae RCV001326745 SCV001517792 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 5 2020-09-13 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the last exon of the TMEM43 mRNA at codon 341 (p.Arg341*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 60 amino acids of the TMEM43 protein. This variant is present in population databases (rs778127887, ExAC 0.02%) but has not been reported in the literature in individuals with a TMEM43-related disease. ClinVar contains an entry for this variant (Variation ID: 217494). This variant would result in the deletion of the C-terminus region of the TMEM43 protein, that includes missense variants reported in individuals affected with arrhythmogenic right ventricular cardiomyopathy. One of these variants (p.Ser358Leu) has been demonstrated to be deleterious (PMID: 18313022, 23812740, 25343256), suggesting that loss of the C-terminal region of TMEM43 is detrimental for protein function. In summary, this variant is a rare nonsense variant that is expected to delete a region of the TMEM43 protein that may be important for protein function. However, in the absence of confirmed segregation or functional studies, at this time this change has been classified as a Variant of Uncertain Significance.

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