NM_005477.3(HCN4):c.3583G>T (p.Val1195Leu) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 3, 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:: RCV002339811.2

Allele description [Variation Report for NM_005477.3(HCN4):c.3583G>T (p.Val1195Leu)]

NM_005477.3(HCN4):c.3583G>T (p.Val1195Leu)

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.3583G>T (p.Val1195Leu)

HGVS:

NC_000015.10:g.73322510C>A
NG_009063.1:g.51755G>T
NM_005477.3:c.3583G>TMANE SELECT
NP_005468.1:p.Val1195Leu
NC_000015.9:g.73614851C>A
NM_005477.2:c.3583G>T

Protein change:

V1195L

Molecular consequence:

NM_005477.3:c.3583G>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002619272	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 3, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002619272

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 3, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Citations

PubMed

A Functional Assay for Sick Sinus Syndrome Genetic Variants.

Jou CJ, Arrington CB, Barnett S, Shen J, Cho S, Sheng X, McCullagh PC, Bowles NE, Pribble CM, Saarel EV, Pilcher TA, Etheridge SP, Tristani-Firouzi M.

Cell Physiol Biochem. 2017;42(5):2021-2029. doi: 10.1159/000479897. Epub 2017 Aug 11.

PubMed [citation]

PMID:: 28803248

Details of each submission

From Ambry Genetics, SCV002619272.2

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

Description

The p.V1195L variant (also known as c.3583G>T), located in coding exon 8 of the HCN4 gene, results from a G to T substitution at nucleotide position 3583. The valine at codon 1195 is replaced by leucine, an amino acid with highly similar properties. In vivo studies suggest this alteration does not impact protein function (Jou CJ et al. Cell Physiol Biochem, 2017 Aug;42:2021-2029). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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: May 1, 2024

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