NM_000238.4(KCNH2):c.1883del (p.Gly628fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 7, 2015
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:: RCV000478962.3

Allele description [Variation Report for NM_000238.4(KCNH2):c.1883del (p.Gly628fs)]

NM_000238.4(KCNH2):c.1883del (p.Gly628fs)

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.1883del (p.Gly628fs)

HGVS:

NC_000007.14:g.150951511del
NG_008916.1:g.31417del
NM_000238.4:c.1883delMANE SELECT
NM_001204798.2:c.863del
NM_001406753.1:c.1594delG
NM_001406755.1:c.1705delG
NM_001406756.1:c.1594delG
NM_001406757.1:c.1582delG
NM_172056.3:c.1882delG
NM_172057.3:c.863del
NP_000229.1:p.Gly628Alafs
NP_000229.1:p.Gly628fs
NP_001191727.1:p.Gly288fs
NP_001393682.1:p.Gly532Alafs
NP_001393684.1:p.Gly569Alafs
NP_001393685.1:p.Gly532Alafs
NP_001393686.1:p.Gly528Alafs
NP_742053.1:p.Gly628Alafs
NP_742053.1:p.Gly628fs
NP_742054.1:p.Gly288Alafs
NP_742054.1:p.Gly288fs
LRG_288t1:c.1882del
LRG_288t2:c.1883del
LRG_288t3:c.862del
LRG_288:g.31417del
LRG_288p1:p.Gly628Alafs
LRG_288p2:p.Gly628fs
LRG_288p3:p.Gly288Alafs
NC_000007.13:g.150648599del
NM_000238.2:c.1883delG
NM_000238.3:c.1882delG
NM_172056.2:c.1883del
NM_172057.2:c.862delG
NR_176254.1:n.2290delG
NR_176255.1:n.1163delG

Protein change:

G288fs

Links:

dbSNP: rs1064793855

NCBI 1000 Genomes Browser:

rs1064793855

Molecular consequence:

NM_000238.4:c.1883del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001204798.2:c.863del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406753.1:c.1594delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406755.1:c.1705delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406756.1:c.1594delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406757.1:c.1582delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172056.3:c.1882delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172057.3:c.863del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000567187	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jul 7, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000567187

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jul 7, 2015)

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, SCV000567187.3

#	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.1883delG deletion in the KCNH2 gene has not been reported to our knowledge, thisvariant causes a shift in reading frame starting at codon Glycine 628, changing it to an Alanine, andcreating a premature stop codon at position 86 of the new reading frame, denoted p.Gly628AlafsX86. Thisdeletion is expected to result in either an abnormal, truncated protein product or loss of protein from thisallele through nonsense-mediated mRNA decay. Other frameshift variants in the KCNH2 gene havebeen reported in HGMD in association with LQTS (Stenson P et al., 2014). Furthermore, the c.1883delGvariant was not observed in approximately 6,500 individuals of European and African American ancestryin the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, c.1883delG 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: Nov 5, 2022

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