NM_000238.4(KCNH2):c.678del (p.Ala228fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 16, 2018
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:: RCV000182055.4

Allele description [Variation Report for NM_000238.4(KCNH2):c.678del (p.Ala228fs)]

NM_000238.4(KCNH2):c.678del (p.Ala228fs)

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.678del (p.Ala228fs)

HGVS:

NC_000007.14:g.150958299del
NG_008916.1:g.24630del
NM_000238.4:c.678delMANE SELECT
NM_001406753.1:c.388delG
NM_001406755.1:c.499delG
NM_001406756.1:c.388delG
NM_001406757.1:c.376delG
NM_172056.3:c.676delG
NP_000229.1:p.Ala228Argfs
NP_000229.1:p.Ala228fs
NP_001393682.1:p.Ala132Argfs
NP_001393684.1:p.Ala169Argfs
NP_001393685.1:p.Ala132Argfs
NP_001393686.1:p.Ala128Argfs
NP_742053.1:p.Ala228Argfs
NP_742053.1:p.Ala228fs
LRG_288t1:c.676del
LRG_288t2:c.678del
LRG_288:g.24630del
LRG_288p1:p.Ala228Argfs
LRG_288p2:p.Ala228fs
NC_000007.13:g.150655385del
NC_000007.13:g.150655387del
NM_000238.2:c.678delG
NM_000238.3:c.676delG
NM_000238.3:c.678delG
NM_172056.2:c.678del
NR_176254.1:n.1084delG
p.A228RfsX132

Protein change:

A228fs

Links:

dbSNP: rs794728496

NCBI 1000 Genomes Browser:

rs794728496

Molecular consequence:

NM_000238.4:c.678del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406753.1:c.388delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406755.1:c.499delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406756.1:c.388delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406757.1:c.376delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172056.3:c.676delG - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000234358	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jul 16, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000234358

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jul 16, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000234358.9

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

Description

Although the c.678delG pathogenic variant in the KCNH2 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon alanine 228, changing it to an arginine, and creating a premature stop codon at position 132 of the new reading frame, denoted p.Ala228ArgfsX132. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the KCNH2 gene have been reported in Human Gene Mutation Database in association with LQTS (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.678delG variant has not been observed in large population cohorts (Lek et al., 2016). In summary, c.678delG in the KCNH2 gene is interpreted as a pathogenic variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 9, 2024

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