NM_000218.3(KCNQ1):c.707T>G (p.Leu236Arg) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 27, 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:: RCV000182304.4

Allele description [Variation Report for NM_000218.3(KCNQ1):c.707T>G (p.Leu236Arg)]

NM_000218.3(KCNQ1):c.707T>G (p.Leu236Arg)

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_000218.3(KCNQ1):c.707T>G (p.Leu236Arg)

Other names:

p.L236R:CTG>CGG

HGVS:

NC_000011.10:g.2572036T>G
NG_008935.1:g.132046T>G
NM_000218.3:c.707T>GMANE SELECT
NM_001406836.1:c.707T>G
NM_001406837.1:c.437T>G
NM_181798.2:c.326T>G
NP_000209.2:p.Leu236Arg
NP_000209.2:p.Leu236Arg
NP_001393765.1:p.Leu236Arg
NP_001393766.1:p.Leu146Arg
NP_861463.1:p.Leu109Arg
NP_861463.1:p.Leu109Arg
LRG_287t1:c.707T>G
LRG_287t2:c.326T>G
LRG_287:g.132046T>G
LRG_287p1:p.Leu236Arg
LRG_287p2:p.Leu109Arg
NC_000011.9:g.2593266T>G
NM_000218.2:c.707T>G
NM_181798.1:c.326T>G
NR_040711.2:n.600T>G

Protein change:

L109R

Links:

dbSNP: rs794728512

NCBI 1000 Genomes Browser:

rs794728512

Molecular consequence:

NM_000218.3:c.707T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.707T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406837.1:c.437T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181798.2:c.326T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

Recent activity

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misshapen-like kinase 1 isoform 3 [Homo sapiens]
misshapen-like kinase 1 isoform 3 [Homo sapiens]
gi|27436917|ref|NP_722549.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000234607	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Mar 27, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000234607

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Mar 27, 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, SCV000234607.13

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

Description

This missense change is denoted Leu236Arg (aka L236R) at the protein level and c.707 T>G at the cDNA level. The Leu236Arg variant in the KCNQ1 gene has not been previously published as a disease-causing mutation or as a benign polymorphism to our knowledge. Leu236Arg results in a non-conservative amino acid substitution of a non-polar Leucine with a positively-charged Arginine at a position that is conserved throughout evolution.In silico analysis predicts Leu236Arg is probably damaging to protein structure/function (Adzhubei IA et al., 2010, Kumar P et al., 2009, Schwarz JM et al., 2010). In addition,mutations in surrounding codons (Arg231Cys, Arg231His, Ile235Asn, Leu239Pro) have been reported in association with LQTS, further supporting the functional importance of this region of the protein. Finally, Leu236Arg was not detected in 650 control alleles from individuals of various ethnic backgrounds tested at GeneDx, indicating it is not a common benign variant in these populations of individuals. With the clinical and molecular information available at this time, we cannot unequivocally determine the clinical significance of Leu236Arg in the KCNQ1 gene, although it is a good candidate for a disease-causing mutation.The variant is found in LQT panel(s).

#	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: Mar 26, 2023

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