Submissions for variant NM_005477.3(HCN4):c.1683C>A (p.Gly561=)

gnomAD frequency: 0.01030  dbSNP: rs62641690

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000170928	SCV000223487	benign	not specified	2014-06-18	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.
Invitae	RCV001085024	SCV000288898	benign	Brugada syndrome 8	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000619178	SCV000735186	benign	Cardiovascular phenotype	2015-08-07	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Athena Diagnostics Inc	RCV000711883	SCV000842294	benign	not provided	2018-05-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001115974	SCV001273991	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000170928	SCV004804272	benign	not specified	2024-01-08	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000711883	SCV001978249	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000170928	SCV001979307	benign	not specified		no assertion criteria provided	clinical testing