Submissions for variant NM_017636.4(TRPM4):c.1376G>A (p.Arg459His)

gnomAD frequency: 0.00086  dbSNP: rs142312281

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000538128	SCV000646085	likely benign	Progressive familial heart block type IB	2025-01-27	criteria provided, single submitter	clinical testing
Center for Personalized Medicine, Children's Hospital Los Angeles	RCV003317271	SCV000692557	uncertain significance	not provided	2016-02-19	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002384174	SCV002699504	likely benign	Cardiovascular phenotype	2019-11-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
GeneDx	RCV003317271	SCV004021586	uncertain significance	not provided	2023-01-12	criteria provided, single submitter	clinical testing	Identified in a patient with reported history of bradycardia, failure to thrive, hypoxemia, hypsarrhythmia, PFO, seizures, and tachycardia (Ji et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30755392)
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV005404678	SCV006065784	likely benign	not specified	2025-04-09	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004541720	SCV004764293	likely benign	TRPM4-related disorder	2020-09-25	no assertion criteria provided	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).