NM_005477.3(HCN4):c.3497_3500del (p.Ser1166fs) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 29, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002453582.3

Allele description [Variation Report for NM_005477.3(HCN4):c.3497_3500del (p.Ser1166fs)]

NM_005477.3(HCN4):c.3497_3500del (p.Ser1166fs)

Gene:

HCN4:hyperpolarization activated cyclic nucleotide gated potassium channel 4 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q24.1

Genomic location:

Preferred name:

NM_005477.3(HCN4):c.3497_3500del (p.Ser1166fs)

HGVS:

NC_000015.10:g.73322594_73322597del
NC_000015.9:g.73614934_73614937del
NG_009063.1:g.51669_51672del
NM_005477.3:c.3497_3500delMANE SELECT
NP_005468.1:p.Ser1166fs
NC_000015.9:g.73614934_73614937del
NC_000015.9:g.73614934_73614937delAAAG
NC_000015.9:g.73614935_73614938del
NM_005477.2:c.3497_3500del
NM_005477.2:c.3497_3500delCTTT
p.S1166CfsX14
p.Ser1166CysfsX14

Protein change:

S1166fs

Links:

dbSNP: rs774674047

NCBI 1000 Genomes Browser:

rs774674047

Molecular consequence:

NM_005477.3:c.3497_3500del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002617252	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 29, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002617252

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 29, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Ambry Genetics, SCV002617252.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The c.3497_3500delCTTT variant, located in coding exon 8 of the HCN4 gene, results from a deletion of 4 nucleotides at nucleotide positions 3497 to 3500, causing a translational frameshift with a predicted alternate stop codon (p.S1166Cfs*14). This alteration occurs at the 3' terminus of theHCN4 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 38 amino acids (3%) of the protein. The exact functional effect of this alteration is unknown. In addition, loss of function of HCN4 has not been established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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