NM_000238.4(KCNH2):c.2724_2728dup (p.Pro910fs) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 11, 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:: RCV000631709.4

Allele description [Variation Report for NM_000238.4(KCNH2):c.2724_2728dup (p.Pro910fs)]

NM_000238.4(KCNH2):c.2724_2728dup (p.Pro910fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_000238.4(KCNH2):c.2724_2728dup (p.Pro910fs)

HGVS:

NC_000007.14:g.150947843_150947847dup
NG_008916.1:g.35080_35084dup
NM_000238.4:c.2724_2728dupMANE SELECT
NM_172057.3:c.1704_1708dup
NP_000229.1:p.Pro910fs
NP_742054.1:p.Pro570fs
LRG_288:g.35080_35084dup
NC_000007.13:g.150644930_150644931insGCCCC
NC_000007.13:g.150644931_150644935dup
NC_000007.14:g.150947842_150947843insGCCCC
NM_000238.2:c.2724_2728dup
NM_000238.2:c.2724_2728dupGGGGC
NM_000238.3:c.2724_2728dupGGGGC
p.P910RfsX66

Protein change:

P570fs

Links:

dbSNP: rs794728449

NCBI 1000 Genomes Browser:

rs794728449

Molecular consequence:

NM_000238.4:c.2724_2728dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172057.3:c.1704_1708dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

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putative secreted protein [Streptomyces scabiei 87.22]
putative secreted protein [Streptomyces scabiei 87.22]
gi|260645985|emb|CBG69076.1|

Protein
RecName: Full=Valacyclovir hydrolase; Short=VACVase; Short=Valacyclovirase; AltN...
RecName: Full=Valacyclovir hydrolase; Short=VACVase; Short=Valacyclovirase; AltName: Full=Biphenyl hydrolase-like protein; AltName: Full=Biphenyl hydrolase-related protein; Short=Bph-rp; AltName: Full=Breast epithelial mucin-associated antigen; Short=MCNAA; Flags: Precursor
gi|39931107|sp|Q86WA6.1|BPHL_HUMAN

Protein
LOC125599921 [Brassica napus]
LOC125599921 [Brassica napus]
Gene ID:125599921

Gene
AMT [Strigops habroptila]
AMT [Strigops habroptila]
Gene ID:115614213

Gene
LOC106439791 [Brassica napus]
LOC106439791 [Brassica napus]
Gene ID:106439791

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000752796	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 11, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 34319147, 10973849, 19862833, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000752796

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 11, 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

Rare Coding Variants Associated With Electrocardiographic Intervals Identify Monogenic Arrhythmia Susceptibility Genes: A Multi-Ancestry Analysis.

Choi SH, Jurgens SJ, Haggerty CM, Hall AW, Halford JL, Morrill VN, Weng LC, Lagerman B, Mirshahi T, Pettinger M, Guo X, Lin HJ, Alonso A, Soliman EZ, Kornej J, Lin H, Moscati A, Nadkarni GN, Brody JA, Wiggins KL, Cade BE, Lee J, et al.

Circ Genom Precis Med. 2021 Aug;14(4):e003300. doi: 10.1161/CIRCGEN.120.003300. Epub 2021 Jul 28.

PubMed [citation]

PMID:: 34319147
PMCID:: PMC8373440

Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.

Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT.

Circulation. 2000 Sep 5;102(10):1178-85.

PubMed [citation]

PMID:: 10973849

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000752796.4

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

Description

This premature translational stop signal has been observed in individual(s) with long QT syndrome (PMID: 34319147). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 200660). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro910Argfs*66) in the KCNH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNH2 are known to be pathogenic (PMID: 10973849, 19862833).

#	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: Jun 23, 2024

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