ClinVar Miner

Submissions for variant NM_017636.4(TRPM4):c.1873+3G>T

dbSNP: rs779988026
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues RCV000853593 SCV000996561 uncertain significance Brugada syndrome 2019-04-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV002409009 SCV002723579 uncertain significance Cardiovascular phenotype 2020-01-17 criteria provided, single submitter clinical testing The c.1873+3G>T intronic variant results from a G to T substitution 3 nucleotides after coding exon 13 in the TRPM4 gene. This nucleotide position is not well conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted to weaken (but not abolish) the efficiency of the native splice donor site by ESEfinder, while BDGP does not produce a reliable prediction for the nearby native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV002536199 SCV003325248 uncertain significance Progressive familial heart block type IB 2022-03-09 criteria provided, single submitter clinical testing This sequence change falls in intron 13 of the TRPM4 gene. It does not directly change the encoded amino acid sequence of the TRPM4 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs779988026, gnomAD 0.0009%). 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: 692250). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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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