ClinVar Miner

Submissions for variant NM_024334.2(TMEM43):c.661C>T (p.Arg221Cys) (rs182464375)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183938 SCV000236430 uncertain significance not provided 2013-09-24 criteria provided, single submitter clinical testing p.Arg221Cys (CGT>TGT): c.661 C>T in exon 8 of the TMEM43 gene (NM_024334.2). The R221C variant in the TMEM43 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. R221C results in a non-conservative amino acid substitution of a positively charged Arginine residue with a neutral, polar Cysteine residue at a position that is not conserved through evolution. In silico analysis was inconsistent with regard to the effect this variant may have on the protein structure/function. The R221C variant was observed in 2/120 (1.7%) alleles of individuals with Colombian ethnic background identified in the 1000 genomes project (Kersey P et al., 2010). With the clinical and molecular information available at this time, we cannot definitively determine if R221C in TMEM43 is a disease-causing mutation or rare benign variant. The variant is found in ARVC panel(s).
Color RCV001180050 SCV001344899 uncertain significance Cardiomyopathy 2020-03-04 criteria provided, single submitter clinical testing
Invitae RCV001243981 SCV001417173 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 5 2019-09-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 221 of the TMEM43 protein (p.Arg221Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs182464375, ExAC 0.03%). This variant has not been reported in the literature in individuals with TMEM43-related conditions. ClinVar contains an entry for this variant (Variation ID: 202118). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; 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.

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.