Submissions for variant NM_005477.3(HCN4):c.2181C>T (p.His727=)

gnomAD frequency: 0.00036  dbSNP: rs140354126

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079630	SCV000288900	likely benign	Brugada syndrome 8	2025-01-29	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000726222	SCV000342994	uncertain significance	not provided	2016-07-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000726222	SCV000517071	likely benign	not provided	2020-08-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000618542	SCV000738048	likely benign	Cardiovascular phenotype	2017-06-08	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.
Clinical Genetics, Academic Medical Center	RCV000345368	SCV001922303	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000726222	SCV001954684	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000726222	SCV001965149	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004739632	SCV005353486	likely benign	HCN4-related disorder	2024-08-26	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).