Submissions for variant NM_005477.3(HCN4):c.1518C>T (p.Tyr506=)

gnomAD frequency: 0.00163  dbSNP: rs139590882

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000178242	SCV000168799	benign	not specified	2014-04-28	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)	RCV000178242	SCV000230286	benign	not specified	2015-03-12	criteria provided, single submitter	clinical testing
Invitae	RCV000227507	SCV000288897	benign	Brugada syndrome 8	2024-02-01	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000178242	SCV000613588	benign	not specified	2017-06-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621555	SCV000735124	likely benign	Cardiovascular phenotype	2015-08-27	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.
Illumina Laboratory Services, Illumina	RCV001115977	SCV001273995	benign	Sick sinus syndrome 2, autosomal dominant	2018-01-13	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000178242	SCV004122620	benign	not specified	2023-10-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001528998	SCV004132797	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	HCN4: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV004530084	SCV004737576	benign	HCN4-related disorder	2019-09-18	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528998	SCV001741703	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000178242	SCV001923871	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000178242	SCV001953210	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528998	SCV001975066	likely benign	not provided		no assertion criteria provided	clinical testing