NM_005477.3(HCN4):c.2648C>G (p.Pro883Arg) AND Sick sinus syndrome 2, autosomal dominant

Germline classification:: Benign/Likely benign (2 submissions)
Last evaluated:: Aug 1, 2017
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000578029.5

Allele description [Variation Report for NM_005477.3(HCN4):c.2648C>G (p.Pro883Arg)]

NM_005477.3(HCN4):c.2648C>G (p.Pro883Arg)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

15q24.1

Genomic location:

Preferred name:

NM_005477.3(HCN4):c.2648C>G (p.Pro883Arg)

Other names:

p.P883R:CCC>CGC

HGVS:

NC_000015.10:g.73323445G>C
NG_009063.1:g.50820C>G
NM_005477.3:c.2648C>GMANE SELECT
NP_005468.1:p.Pro883Arg
NC_000015.9:g.73615786G>C
NM_005477.2:c.2648C>G

Protein change:

P883R

Links:

dbSNP: rs148398509

NCBI 1000 Genomes Browser:

rs148398509

Molecular consequence:

NM_005477.3:c.2648C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Sick sinus syndrome 2, autosomal dominant (SSS2)
Synonyms:: ATRIAL FIBRILLATION WITH BRADYARRHYTHMIA; SINUS BRADYCARDIA SYNDROME, FAMILIAL, AUTOSOMAL DOMINANT; SINUS NODE DISEASE, FAMILIAL, AUTOSOMAL DOMINANT; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008102; MedGen: C1834144; Orphanet: 166282; OMIM: 163800

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000679913	Phosphorus, Inc.	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Aug 1, 2017)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23861362, 25145518, 27173043, 28104484, 25741868
SCV001277259	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Apr 28, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25145518, 25642760 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000679913

Phosphorus, Inc.

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Aug 1, 2017)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV001277259

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Likely benign
(Apr 28, 2017)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Interpreting secondary cardiac disease variants in an exome cohort.

Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program..

Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16.

PubMed [citation]

PMID:: 23861362
PMCID:: PMC3887521

Dilation of the Aorta Ascendens Forms Part of the Clinical Spectrum of HCN4 Mutations.

Vermeer AMC, Lodder EM, Thomas D, Duijkers FAM, Marcelis C, van Gorselen EOF, Fortner P, Buss SJ, Mereles D, Katus HA, Wilde AAM, Bezzina CR, Boekholdt SM, Schweizer PA, Christiaans I.

J Am Coll Cardiol. 2016 May 17;67(19):2313-2315. doi: 10.1016/j.jacc.2016.01.086. No abstract available.

PubMed [citation]

PMID:: 27173043

See all PubMed Citations (6)

Details of each submission

From Phosphorus, Inc., SCV000679913.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (5)

#	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		1	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV001277259.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

#	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: May 7, 2024

ClinVar

Relating variation to medicine