Submissions for variant NM_005477.3(HCN4):c.2537C>T (p.Pro846Leu)

gnomAD frequency: 0.00005  dbSNP: rs747467877

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000456750	SCV000541552	likely benign	Brugada syndrome 8	2023-11-20	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000711885	SCV000842296	uncertain significance	not provided	2017-12-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003168728	SCV003912956	uncertain significance	Cardiovascular phenotype	2023-02-07	criteria provided, single submitter	clinical testing	The p.P846L variant (also known as c.2537C>T), located in coding exon 8 of the HCN4 gene, results from a C to T substitution at nucleotide position 2537. The proline at codon 846 is replaced by leucine, an amino acid with similar properties. This variant was detected in a cardiomyopathy/arrhythmia genetic testing cohort; however, clinical details were limited, and additional cardiac variants were detected in some cases (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Clinical Genetics, Academic Medical Center	RCV000711885	SCV001920984	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000711885	SCV001963557	uncertain significance	not provided		no assertion criteria provided	clinical testing