NM_000238.4(KCNH2):c.1921_1923del (p.Ser641del) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 14, 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:: RCV003018064.3

Allele description [Variation Report for NM_000238.4(KCNH2):c.1921_1923del (p.Ser641del)]

NM_000238.4(KCNH2):c.1921_1923del (p.Ser641del)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_000238.4(KCNH2):c.1921_1923del (p.Ser641del)

HGVS:

NC_000007.14:g.150951471_150951473del
NG_008916.1:g.31455_31457del
NM_000238.4:c.1921_1923delMANE SELECT
NM_001204798.2:c.901_903del
NM_001406753.1:c.1632_1634delCTC
NM_001406755.1:c.1743_1745delCTC
NM_001406756.1:c.1632_1634delCTC
NM_001406757.1:c.1620_1622delCTC
NM_172056.3:c.1920_1922delCTC
NM_172057.3:c.901_903del
NP_000229.1:p.Ser641del
NP_000229.1:p.Ser641del
NP_001191727.1:p.Ser301del
NP_001393682.1:p.Ser545del
NP_001393684.1:p.Ser582del
NP_001393685.1:p.Ser545del
NP_001393686.1:p.Ser541del
NP_742053.1:p.Ser641del
NP_742053.1:p.Ser641del
NP_742054.1:p.Ser301del
NP_742054.1:p.Ser301del
LRG_288t1:c.1920_1922del
LRG_288t2:c.1921_1923del
LRG_288t3:c.900_902del
LRG_288:g.31455_31457del
LRG_288p1:p.Ser641del
LRG_288p2:p.Ser641del
LRG_288p3:p.Ser301del
NC_000007.13:g.150648558_150648560del
NC_000007.13:g.150648559_150648561del
NM_000238.3:c.1920_1922delCTC
NM_172056.2:c.1921_1923del
NM_172057.2:c.900_902delCTC
NR_176254.1:n.2328_2330delCTC
NR_176255.1:n.1201_1203delCTC

Protein change:

S301del

Molecular consequence:

NM_000238.4:c.1921_1923del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001204798.2:c.901_903del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172057.3:c.901_903del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001406753.1:c.1632_1634delCTC - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001406755.1:c.1743_1745delCTC - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001406756.1:c.1632_1634delCTC - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001406757.1:c.1620_1622delCTC - inframe_indel - [Sequence Ontology: SO:0001820]
NM_172056.3:c.1920_1922delCTC - inframe_indel - [Sequence Ontology: SO:0001820]

Condition(s)

Name:: Long QT syndrome (LQTS)
Identifiers:: MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003304754	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 14, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18441445, 22949429, 25417810, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003304754

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 14, 2023)

germline

clinical testing

PubMed (4)
[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

Mutation site dependent variability of cardiac events in Japanese LQT2 form of congenital long-QT syndrome.

Nagaoka I, Shimizu W, Itoh H, Yamamoto S, Sakaguchi T, Oka Y, Tsuji K, Ashihara T, Ito M, Yoshida H, Ohno S, Makiyama T, Miyamoto Y, Noda T, Kamakura S, Akao M, Horie M.

Circ J. 2008 May;72(5):694-9.

PubMed [citation]

PMID:: 18441445

Phylogenetic and physicochemical analyses enhance the classification of rare nonsynonymous single nucleotide variants in type 1 and 2 long-QT syndrome.

Giudicessi JR, Kapplinger JD, Tester DJ, Alders M, Salisbury BA, Wilde AA, Ackerman MJ.

Circ Cardiovasc Genet. 2012 Oct 1;5(5):519-28. doi: 10.1161/CIRCGENETICS.112.963785. Epub 2012 Sep 4.

PubMed [citation]

PMID:: 22949429
PMCID:: PMC3705705

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003304754.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant, c.1921_1923del, results in the deletion of 1 amino acid(s) of the KCNH2 protein (p.Ser641del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KCNH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2088283). This variant disrupts a region of the KCNH2 protein in which other variant(s) (p.Ser641Phe) have been determined to be pathogenic (PMID: 18441445, 22949429, 25417810; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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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