ClinVar Miner

Submissions for variant NM_024334.2(TMEM43):c.344T>C (p.Leu115Pro) (rs376182664)

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 RCV000183953 SCV000236446 uncertain significance not provided 2017-09-25 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TMEM43 gene. The L115P variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The L115P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity.
Invitae RCV001069329 SCV001234489 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 5 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 115 of the TMEM43 protein (p.Leu115Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs376182664, ExAC 0.005%). This variant has not been reported in the literature in individuals with TMEM43-related conditions. ClinVar contains an entry for this variant (Variation ID: 202129). 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: "Deleterious"; PolyPhen-2: "Probably 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.
Color RCV001181146 SCV001346240 uncertain significance Cardiomyopathy 2019-04-14 criteria provided, single submitter 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.