Submissions for variant NM_017636.4(TRPM4):c.923C>T (p.Ala308Val)

gnomAD frequency: 0.00001  dbSNP: rs747192078

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000470793	SCV000549933	uncertain significance	Progressive familial heart block type IB	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 308 of the TRPM4 protein (p.Ala308Val). This variant is present in population databases (rs747192078, gnomAD 0.03%). 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: 409639). 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.
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	RCV000523091	SCV000616619	uncertain significance	Brugada syndrome	2017-05-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001753892	SCV002005409	uncertain significance	not provided	2022-07-18	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Ambry Genetics	RCV002374785	SCV002687944	uncertain significance	Cardiovascular phenotype	2024-10-21	criteria provided, single submitter	clinical testing	The p.A308V variant (also known as c.923C>T), located in coding exon 8 of the TRPM4 gene, results from a C to T substitution at nucleotide position 923. The alanine at codon 308 is replaced by valine, an amino acid with similar properties. This alteration has been reported in exome cohorts in individuals of Asian descent (Kim J et al. Sci Rep, 2018 04;8:5677; Wang D et al. Am J Hum Genet, 2018 05;102:794-805). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV001753892	SCV004142175	uncertain significance	not provided	2023-01-01	criteria provided, single submitter	clinical testing