Submissions for variant NM_005477.3(HCN4):c.3337A>G (p.Met1113Val)

gnomAD frequency: 0.00983  dbSNP: rs142735148

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000153351	SCV000168805	benign	not specified	2014-02-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Eurofins Ntd Llc (ga)	RCV000153351	SCV000202835	benign	not specified	2016-01-26	criteria provided, single submitter	clinical testing
Invitae	RCV000232104	SCV000288910	benign	Brugada syndrome 8	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000153351	SCV000311093	benign	not specified		criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000153351	SCV000613593	benign	not specified	2017-06-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000618938	SCV000735223	benign	Cardiovascular phenotype	2015-08-17	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852705	SCV000995419	benign	Cardiomyopathy	2017-09-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001117320	SCV001275496	benign	Sick sinus syndrome 2, autosomal dominant	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Fulgent Genetics, Fulgent Genetics	RCV002477330	SCV002803106	benign	Sick sinus syndrome 2, autosomal dominant; Brugada syndrome 8; Epilepsy, idiopathic generalized, susceptibility to, 18	2021-08-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000153351	SCV003928220	likely benign	not specified	2023-04-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003311683	SCV004010387	benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	HCN4: BS1, BS2
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003311683	SCV004564035	benign	not provided	2023-10-16	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000153351	SCV001925740	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000153351	SCV001957613	benign	not specified		no assertion criteria provided	clinical testing