ClinVar Miner

Submissions for variant NM_024334.2(TMEM43):c.644A>C (p.His215Pro) (rs730880225)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000537954 SCV000642104 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 5 2019-11-26 criteria provided, single submitter clinical testing This sequence change replaces histidine with proline at codon 215 of the TMEM43 protein (p.His215Pro). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and proline. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TMEM43-related disease. ClinVar contains an entry for this variant (Variation ID: 180542). 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. 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756786 SCV000884696 uncertain significance not provided 2018-03-20 criteria provided, single submitter clinical testing The TMEM43 c.644A>C; p.His215Pro variant (rs730880225, ClinVar variant ID 180542), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is absent from the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The histidine at position 215 is highly conserved, considering 11 species, and computational analyses of the effects of the p.His215Pro variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.His215Pro variant cannot be determined with certainty.
Color RCV001176788 SCV001340843 uncertain significance Cardiomyopathy 2019-01-09 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000157521 SCV000207266 uncertain significance Long QT syndrome 2014-10-06 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.