Submissions for variant NM_005477.3(HCN4):c.2804C>T (p.Ser935Phe)

dbSNP: rs775803239

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000726145	SCV000223503	likely benign	not provided	2020-12-15	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000726145	SCV000342387	uncertain significance	not provided	2016-06-10	criteria provided, single submitter	clinical testing
Invitae	RCV000989357	SCV000541557	likely benign	Brugada syndrome 8	2023-12-21	criteria provided, single submitter	clinical testing
Mendelics	RCV000989357	SCV001139652	uncertain significance	Brugada syndrome 8	2019-05-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002433736	SCV002747440	likely benign	Cardiovascular phenotype	2022-01-20	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Stanford Center for Inherited Cardiovascular Disease, Stanford University	RCV000223698	SCV000280106	uncertain significance	not specified	2014-07-30	no assertion criteria provided	clinical testing	Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. HCN4 p.Ser935Phe Given that the variant is novel, there is a lack of population frequency data, and the gene-phenotype association is unclear, we consider this variant a variant of uncertain significance. To the best of our knowledge the variant is novel. In silico analysis with PolyPhen-2 predicts the variant to be benign. The serine at codon 935 is not completely conserved across species. In total the variant has not been seen in ~6500 individuals from publicly available population datasets. There is no variation at codon 935 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6500 Caucasian and African American individuals (as of July 29th, 2014). There is also no variation at this codon listed in dbSNP (as of July 29th, 2014).