ClinVar Miner

Submissions for variant NM_017636.4(TRPM4):c.1637C>T (p.Ser546Leu)

gnomAD frequency: 0.00001  dbSNP: rs764385592
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000558129 SCV000646087 uncertain significance Progressive familial heart block type IB 2024-06-13 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 546 of the TRPM4 protein (p.Ser546Leu). 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 missense change has been observed in individual(s) with clinical features of TRPM4-related conditions (PMID: 32508047). ClinVar contains an entry for this variant (Variation ID: 468929). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine 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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