ClinVar Miner

Submissions for variant NM_017636.4(TRPM4):c.1559C>G (p.Pro520Arg)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002405363 SCV002708871 uncertain significance Cardiovascular phenotype 2021-01-25 criteria provided, single submitter clinical testing The p.P520R variant (also known as c.1559C>G), located in coding exon 11 of the TRPM4 gene, results from a C to G substitution at nucleotide position 1559. The proline at codon 520 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species, and arginine is the reference amino acid in other 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003502666 SCV004268137 uncertain significance Progressive familial heart block type IB 2024-11-27 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 520 of the TRPM4 protein (p.Pro520Arg). 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: 1775210). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The arginine 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.

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