Submissions for variant NM_017636.4(TRPM4):c.308A>G (p.Tyr103Cys)

gnomAD frequency: 0.00041  dbSNP: rs144781529

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV000208070	SCV000264269	likely benign	not specified	2015-06-29	criteria provided, single submitter	clinical testing
Invitae	RCV001082907	SCV000290323	likely benign	Progressive familial heart block type IB	2024-01-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000617330	SCV000735557	likely benign	Cardiovascular phenotype	2020-03-06	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000231318	SCV001151975	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	TRPM4: BS1
Illumina Laboratory Services, Illumina	RCV001082907	SCV001295589	uncertain significance	Progressive familial heart block type IB	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx	RCV000231318	SCV001780565	likely benign	not provided	2021-05-01	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27527004, 25416190, 26636822, 21887725)
Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations	RCV003448288	SCV004175708	uncertain significance	Brugada syndrome	2023-08-09	criteria provided, single submitter	clinical testing	Heterozygous variant NM_017636:c.308A>G (p.Tyr103Cys) in the TRPM4 gene was found on WES data in male proband (39 y.o., Caucasian) with Brugada Syndrome. No additional rare candidate variants (Class III-V of pathogenicity) were found in this proband. This variant is in The Genome Aggregation Database (gnomAD) v2.1.1 with total MAF 0.0003573 (Date of access 09-08-2023). This variant has been reported in 2 articles in patients with variable phenotypes (PMID: 26636822; 21887725). Most in silico predictors are inconclusive in the results (varsome.com). In accordance with ACMG(2015) criteria this variant is classified as Variant of Uncertain Significance (VUS) with following criteria selected: BS1
PreventionGenetics, part of Exact Sciences	RCV003917853	SCV004734487	likely benign	TRPM4-related condition	2022-07-14	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).