NM_000219.6(KCNE1):c.293G>A (p.Arg98Gln) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 16, 2017
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:: RCV000215133.6

Allele description [Variation Report for NM_000219.6(KCNE1):c.293G>A (p.Arg98Gln)]

NM_000219.6(KCNE1):c.293G>A (p.Arg98Gln)

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.293G>A (p.Arg98Gln)

HGVS:

NC_000021.9:g.34449342C>T
NG_009091.1:g.66974G>A
NM_000219.6:c.293G>AMANE SELECT
NM_001127668.4:c.293G>A
NM_001127669.4:c.293G>A
NM_001127670.4:c.293G>A
NM_001270402.3:c.293G>A
NM_001270403.2:c.293G>A
NM_001270404.3:c.293G>A
NM_001270405.3:c.293G>A
NP_000210.2:p.Arg98Gln
NP_001121140.1:p.Arg98Gln
NP_001121141.1:p.Arg98Gln
NP_001121142.1:p.Arg98Gln
NP_001257331.1:p.Arg98Gln
NP_001257332.1:p.Arg98Gln
NP_001257333.1:p.Arg98Gln
NP_001257334.1:p.Arg98Gln
LRG_290t1:c.293G>A
LRG_290:g.66974G>A
NC_000021.8:g.35821640C>T
NM_000219.3:c.293G>A

Protein change:

R98Q

Links:

dbSNP: rs150454912

NCBI 1000 Genomes Browser:

rs150454912

Molecular consequence:

NM_000219.6:c.293G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127668.4:c.293G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127669.4:c.293G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127670.4:c.293G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270402.3:c.293G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270403.2:c.293G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270404.3:c.293G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270405.3:c.293G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Homo sapiens family with sequence similarity 22, member F, mRNA (cDNA clone MGC:...
Homo sapiens family with sequence similarity 22, member F, mRNA (cDNA clone MGC:163262 IMAGE:40146421), complete cds
gi|120660127|gb|BC130390.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000271872	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Nov 16, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24561134, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000271872

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Nov 16, 2017)

germline

clinical testing

PubMed (2)
[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	not provided	5	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

Exome sequencing implicates an increased burden of rare potassium channel variants in the risk of drug-induced long QT interval syndrome.

Weeke P, Mosley JD, Hanna D, Delaney JT, Shaffer C, Wells QS, Van Driest S, Karnes JH, Ingram C, Guo Y, Shyr Y, Norris K, Kannankeril PJ, Ramirez AH, Smith JD, Mardis ER, Nickerson D, George AL Jr, Roden DM.

J Am Coll Cardiol. 2014 Apr 15;63(14):1430-7. doi: 10.1016/j.jacc.2014.01.031. Epub 2014 Feb 19.

PubMed [citation]

PMID:: 24561134
PMCID:: PMC4018823

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000271872.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	PubMed (2)

Description

The p.Arg98Gln variant in KCNE1 has been previously reported by our laboratory i n two unrelated Caucasian individuals with hearing loss. This variant has been i dentified in 11/246202 of the total chromosomes by the Genome Aggregation Databa se across several populations (gnomAD, http://gnomad.broadinstitute.org; dbSNP r s150454912). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational predic tion tools and conservation analyses suggest that this variant may not impact th e protein, though this information is not predictive enough to rule out pathogen icity. In summary, the clinical significance of the p.Arg98Gln variant is uncert ain. ACMG/AMP Criteria applied: BP4.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		5	not provided	2	not provided

Last Updated: Oct 20, 2024

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