NM_000218.2(KCNQ1):c.328G>A (p.Val110Ile) AND not specified

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 5, 2017
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000182259.3

Allele description

NM_000218.2(KCNQ1):c.328G>A (p.Val110Ile)

Gene:

KCNQ1:potassium voltage-gated channel subfamily Q member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.2(KCNQ1):c.328G>A (p.Val110Ile)

Other names:

p.V110I:GTC>ATC

HGVS:

NC_000011.10:g.2445426G>A
NG_008935.1:g.5436G>A
NM_000218.2:c.328G>A
NP_000209.2:p.Val110Ile
LRG_287t1:c.328G>A
LRG_287:g.5436G>A
LRG_287p1:p.Val110Ile
NC_000011.9:g.2466656G>A

Protein change:

V110I

Links:

dbSNP: rs199472677

NCBI 1000 Genomes Browser:

rs199472677

Allele Frequency:

0.00008(A), GO-ESP

Molecular consequence:

NM_000218.2:c.328G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000234562	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Jan 5, 2017)	germline	clinical testing	Citation Link,
SCV000271877	Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jun 2, 2015)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 14661677, 21164565, 22949429, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000234562

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Jan 5, 2017)

germline

clinical testing

Citation Link,

SCV000271877

Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jun 2, 2015)

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	not provided	1	1	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome.

Ackerman MJ, Tester DJ, Jones GS, Will ML, Burrow CR, Curran ME.

Mayo Clin Proc. 2003 Dec;78(12):1479-87.

PubMed [citation]

PMID:: 14661677

Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2.

Cordeiro JM, Perez GJ, Schmitt N, Pfeiffer R, Nesterenko VV, Burashnikov E, Veltmann C, Borggrefe M, Wolpert C, Schimpf R, Antzelevitch C.

Can J Physiol Pharmacol. 2010 Dec;88(12):1181-90. doi: 10.1139/Y10-094.

PubMed [citation]

PMID:: 21164565
PMCID:: PMC3076201

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000234562.11

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

Description

The V110I variant has been previously reported in an individual with LQTS, and patch clamp recording from heterologous cells in vitro showed that this mutation decreased current density and prolonged the duration of simulated left ventricular epicardial action potentials (Cordeiro et al., 2010). The V110I variant was not observed with any significant frequency in approximately 6400 individuals of European and African American background reported in the NHLBI Exome Sequencing Project. However, V110I was also reported in 0.5% of apparently healthy individuals (Ackerman et al., 2003). The V110I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Nevertheless, missense mutations in nearby residues (Y111C, L114P, E115G) have been reported in association with LQTS, supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign 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

From Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine, SCV000271877.1

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

Description

The p.Val110Ile variant in KCNQ1 has not been previously reported in individuals with hearing loss or Jervell and Lange-Nielsen syndrome; however, it has been identified in one individual with long QT syndrome (Cordeiro 2010). This variant has also been identified in 8/55006 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs199472677). In vitro functional studies provide some evidence that this variant may impact protein function (Cordeiro 2010); however, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses suggest that the p.Val110Ile variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Val110Ile variant is uncertain.

#	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		1	not provided	1	not provided

Last Updated: Nov 4, 2017

ClinVar

Relating variation to medicine