ClinVar Miner

Submissions for variant NM_017636.4(TRPM4):c.2264G>A (p.Arg755His)

gnomAD frequency: 0.00001  dbSNP: rs751903628
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
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego RCV000852763 SCV000995481 likely benign Ventricular tachycardia 2019-01-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001858513 SCV002168600 uncertain significance Progressive familial heart block type IB 2024-09-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 755 of the TRPM4 protein (p.Arg755His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TRPM4-related conditions. ClinVar contains an entry for this variant (Variation ID: 691739). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV002442789 SCV002733416 uncertain significance Cardiovascular phenotype 2023-10-10 criteria provided, single submitter clinical testing The p.R755H variant (also known as c.2264G>A), located in coding exon 17 of the TRPM4 gene, results from a G to A substitution at nucleotide position 2264. The arginine at codon 755 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.