ClinVar Miner

Submissions for variant NM_017636.4(TRPM4):c.1294G>A (p.Ala432Thr) (rs201907325)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208441 SCV000264271 uncertain significance Brugada syndrome 2015-05-21 criteria provided, single submitter clinical testing
Invitae RCV000029159 SCV000290315 likely benign Progressive familial heart block type 1B 2017-09-06 criteria provided, single submitter clinical testing
GeneDx RCV000443394 SCV000521223 uncertain significance not specified 2016-10-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TRPM4 gene. Using linkage analysis, Liu et al. (2010) observed the A432T variant segregated with right-bundle branch block (RBBB) in at least 20 family members of a large kindred. Although one affected individual did not harbor the A432T variant, the authors concluded that this was a phenocopy based on the uniqueness of the RBBB compared to other affected family members (Liu et al., 2010). A432T was also observed in a Turkish man with incomplete RBBB who also harbored a second variant in the TRPM4 gene (Stallmeyer et al., 2012).The NHLBI Exome Sequencing Project reports A432T was observed in 9/8,600 (0.1%) alleles from individuals of European background, and it was also observed in 18/11,524 (0.15%) alleles from from individuals of Latino background in the Exome Aggregation Consortium (ExAC) data set, indicating it may be a rare benign variant in these populations. However, the A432T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. Although functional studies have been discordant as to whether or not the A432T variant results in gain or loss of protein function, in silico analysis predicts this variant is probably damaging to the protein structure/function (Liu et al., 2010; Syam et al., 2016).
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000029159 SCV000745390 uncertain significance Progressive familial heart block type 1B 2017-11-07 criteria provided, single submitter clinical testing
OMIM RCV000029159 SCV000051804 pathogenic Progressive familial heart block type 1B 2012-01-01 no assertion criteria provided literature only

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.