NM_000238.4(KCNH2):c.38C>A (p.Thr13Asn) AND Cardiac arrhythmia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 20, 2023
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:: RCV001843182.11

Allele description [Variation Report for NM_000238.4(KCNH2):c.38C>A (p.Thr13Asn)]

NM_000238.4(KCNH2):c.38C>A (p.Thr13Asn)

Gene:

KCNH2:potassium voltage-gated channel subfamily H member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_000238.4(KCNH2):c.38C>A (p.Thr13Asn)

HGVS:

NC_000007.14:g.150977876G>T
NG_008916.1:g.5051C>A
NM_000238.4:c.38C>AMANE SELECT
NM_172056.3:c.38C>A
NP_000229.1:p.Thr13Asn
NP_000229.1:p.Thr13Asn
NP_742053.1:p.Thr13Asn
NP_742053.1:p.Thr13Asn
LRG_288t1:c.38C>A
LRG_288t2:c.38C>A
LRG_288t3:c.-22373C>A
LRG_288:g.5051C>A
LRG_288p1:p.Thr13Asn
LRG_288p2:p.Thr13Asn
NC_000007.13:g.150674964G>T
NM_000238.2:c.38C>A
NM_000238.3:c.38C>A
NM_172056.2:c.38C>A
NM_172057.2:c.-22373C>A
NR_176254.1:n.446C>A

Protein change:

T13N

Links:

dbSNP: rs758978727

NCBI 1000 Genomes Browser:

rs758978727

Molecular consequence:

NM_000238.4:c.38C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.38C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_176254.1:n.446C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Cardiac arrhythmia
Synonyms:: Cardiac rhythm disease
Identifiers:: EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001349579	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 20, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26669661, 32893267, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001349579

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 20, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Asymmetry of parental origin in long QT syndrome: preferential maternal transmission of KCNQ1 variants linked to channel dysfunction.

Itoh H, Berthet M, Fressart V, Denjoy I, Maugenre S, Klug D, Mizusawa Y, Makiyama T, Hofman N, Stallmeyer B, Zumhagen S, Shimizu W, Wilde AA, Schulze-Bahr E, Horie M, Tezenas du Montcel S, Guicheney P.

Eur J Hum Genet. 2016 Aug;24(8):1160-6. doi: 10.1038/ejhg.2015.257. Epub 2015 Dec 16.

PubMed [citation]

PMID:: 26669661
PMCID:: PMC4970673

Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.

Walsh R, Lahrouchi N, Tadros R, Kyndt F, Glinge C, Postema PG, Amin AS, Nannenberg EA, Ware JS, Whiffin N, Mazzarotto F, Škorić-Milosavljević D, Krijger C, Arbelo E, Babuty D, Barajas-Martinez H, Beckmann BM, Bézieau S, Bos JM, Breckpot J, Campuzano O, Castelletti S, et al.

Genet Med. 2021 Jan;23(1):47-58. doi: 10.1038/s41436-020-00946-5. Epub 2020 Sep 7.

PubMed [citation]

PMID:: 32893267
PMCID:: PMC7790744

See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001349579.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This missense variant replaces threonine with asparagine at codon 13 of the KCNH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with long QT syndrome (PMID: 26669661, 32893267). This variant has been identified in 21/269462 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	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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