NM_000219.6(KCNE1):c.208A>C (p.Lys70Gln) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 18, 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:: RCV003387912.1

Allele description [Variation Report for NM_000219.6(KCNE1):c.208A>C (p.Lys70Gln)]

NM_000219.6(KCNE1):c.208A>C (p.Lys70Gln)

Gene:

KCNE1:potassium voltage-gated channel subfamily E regulatory subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.12

Genomic location:

Preferred name:

NM_000219.6(KCNE1):c.208A>C (p.Lys70Gln)

HGVS:

NC_000021.9:g.34449427T>G
NG_009091.1:g.66889A>C
NM_000219.6:c.208A>CMANE SELECT
NM_001127668.4:c.208A>C
NM_001127669.4:c.208A>C
NM_001127670.4:c.208A>C
NM_001270402.3:c.208A>C
NM_001270403.2:c.208A>C
NM_001270404.3:c.208A>C
NM_001270405.3:c.208A>C
NP_000210.2:p.Lys70Gln
NP_001121140.1:p.Lys70Gln
NP_001121141.1:p.Lys70Gln
NP_001121142.1:p.Lys70Gln
NP_001257331.1:p.Lys70Gln
NP_001257332.1:p.Lys70Gln
NP_001257333.1:p.Lys70Gln
NP_001257334.1:p.Lys70Gln
LRG_290:g.66889A>C
NC_000021.8:g.35821725T>G
NM_000219.3:c.208A>C
NM_000219.5:c.208A>C

Protein change:

K70Q

Links:

dbSNP: rs1568836235

NCBI 1000 Genomes Browser:

rs1568836235

Molecular consequence:

NM_000219.6:c.208A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127668.4:c.208A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127669.4:c.208A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127670.4:c.208A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001270402.3:c.208A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001270403.2:c.208A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001270404.3:c.208A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001270405.3:c.208A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004099935	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Sep 18, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004099935

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Sep 18, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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

Alteration of channel activities and gating by mutations of slow ISK potassium channel.

Takumi T, Moriyoshi K, Aramori I, Ishii T, Oiki S, Okada Y, Ohkubo H, Nakanishi S.

J Biol Chem. 1991 Nov 25;266(33):22192-8.

PubMed [citation]

PMID:: 1939241

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004099935.1

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

Description

Variant summary: KCNE1 c.208A>C (p.Lys70Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251410 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.208A>C in individuals affected with Long QT Syndrome has been reported. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed this variant mildly impacts protein expression however channel activity was similar to wild type (Takumi_1991). The following publication has been ascertained in the context of this evaluation (PMID: 1939241). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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: May 1, 2024

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