NM_000218.2(KCNQ1):c.613G>A (p.Val205Met) AND Long QT syndrome 1

Clinical significance:Pathogenic (Last evaluated: Jul 1, 2008)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000030815.2

Allele description [Variation Report for NM_000218.2(KCNQ1):c.613G>A (p.Val205Met)]

NM_000218.2(KCNQ1):c.613G>A (p.Val205Met)

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.613G>A (p.Val205Met)
Other names:
KCNQ1 V205M; p.V205M:GTG>ATG
HGVS:
  • NC_000011.10:g.2571333G>A
  • NG_008935.1:g.131343G>A
  • NM_000218.2:c.613G>A
  • NM_181798.1:c.232G>A
  • NP_000209.2:p.Val205Met
  • NP_861463.1:p.Val78Met
  • LRG_287t1:c.613G>A
  • LRG_287t2:c.232G>A
  • LRG_287:g.131343G>A
  • LRG_287p1:p.Val205Met
  • LRG_287p2:p.Val78Met
  • NC_000011.9:g.2592563G>A
  • NP_000209.2:p.V205M
Protein change:
V205M; VAL205MET
Links:
OMIM: 607542.0040; dbSNP: 151344631
NCBI 1000 Genomes Browser:
rs151344631
Allele Frequency:
0.00001(A)
Molecular consequence:
  • NM_000218.2:c.613G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome 1 (LQT1)
Synonyms:
Romano-Ward syndrome
Identifiers:
MedGen: C0035828; Orphanet: 101016; Orphanet: 768; OMIM: 192500

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000053486OMIMno assertion criteria providedPathogenic
(Jul 1, 2008)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A KCNQ1 V205M missense mutation causes a high rate of long QT syndrome in a First Nations community of northern British Columbia: a community-based approach to understanding the impact.

Arbour L, Rezazadeh S, Eldstrom J, Weget-Simms G, Rupps R, Dyer Z, Tibbits G, Accili E, Casey B, Kmetic A, Sanatani S, Fedida D.

Genet Med. 2008 Jul;10(7):545-50. doi: 10.1097GIM.0b013e31817c6b19.

PubMed [citation]
PMID:
18580685

Details of each submission

From OMIM, SCV000053486.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 2 severely affected index cases with long QT syndrome (LQT1; 192500) from a First Nations community in northern British Columbia (Gitxsan), Arbour et al. (2008) identified a G-to-A transition in exon 4 of the KCNQ1 gene that resulted in a val-to-met substitution at codon 205 (V205M). Identification of the mutation prompted the ascertainment of 122 relatives using community-based participatory research principles. The 22 further mutation carriers identified had a significantly higher mean corrected QT interval than noncarriers (465 +/- 28 milliseconds vs 434 +/- 26 milliseconds, P less than 0.0001); however, 30% of carriers had a corrected QT interval below 440 milliseconds. In transfected mouse Itk cells this mutation suppressed I(Ks) by causing a dramatic depolarizing shift in activation voltage coupled with acceleration of channel deactivation. Arbour et al. (2008) concluded that this mutation likely conferred increased susceptibility to arrhythmias because of decreased I(Ks) current. Even with a common mutation within a relatively homogeneous population, clinical expression remains variable, supporting the difficulty of definitive diagnosis without genetic testing.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 13, 2018