ClinVar Miner

Submissions for variant NM_017636.4(TRPM4):c.2894G>A (p.Arg965His)

dbSNP: rs150452571
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001313027 SCV001503502 uncertain significance Progressive familial heart block type IB 2024-06-19 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 965 of the TRPM4 protein (p.Arg965His). This variant is present in population databases (rs150452571, gnomAD 0.02%). This missense change has been observed in individual(s) with sudden unexplained death (PMID: 29247119, 30391667). ClinVar contains an entry for this variant (Variation ID: 1014313). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
GeneDx RCV001560007 SCV001782337 uncertain significance not provided 2021-05-03 criteria provided, single submitter clinical testing Observed in individuals with sudden unexplained death (Lin et al., 2017; Subbotina et al., 2018); Reported in ClinVar but additional evidence is not available (ClinVar Variant ID #1014313; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30391667, 29247119)
Ambry Genetics RCV002437071 SCV002749667 uncertain significance Cardiovascular phenotype 2024-05-29 criteria provided, single submitter clinical testing The p.R965H variant (also known as c.2894G>A), located in coding exon 19 of the TRPM4 gene, results from a G to A substitution at nucleotide position 2894. The arginine at codon 965 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported in association with sudden unexplained death (Lin Y et al. Circ Cardiovasc Genet, 2017 Dec;10; Subbotina E et al. Forensic Sci. Int., 2018 Dec;293:37-46). This amino acid position is well 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.
Fulgent Genetics, Fulgent Genetics RCV002476445 SCV002787186 uncertain significance Progressive familial heart block type IB; Erythrokeratodermia variabilis et progressiva 6 2021-07-07 criteria provided, single submitter clinical testing

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