NM_000238.4(KCNH2):c.26C>T (p.Ala9Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 7, 2019
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:: RCV000181953.13

Allele description [Variation Report for NM_000238.4(KCNH2):c.26C>T (p.Ala9Val)]

NM_000238.4(KCNH2):c.26C>T (p.Ala9Val)

Gene:

KCNH2:potassium voltage-gated channel subfamily H member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_000238.4(KCNH2):c.26C>T (p.Ala9Val)

Other names:

p.A9V:GCG>GTG

HGVS:

NC_000007.14:g.150977888G>A
NG_008916.1:g.5039C>T
NM_000238.4:c.26C>TMANE SELECT
NM_172056.3:c.26C>T
NP_000229.1:p.Ala9Val
NP_000229.1:p.Ala9Val
NP_742053.1:p.Ala9Val
NP_742053.1:p.Ala9Val
LRG_288t1:c.26C>T
LRG_288t2:c.26C>T
LRG_288:g.5039C>T
LRG_288p1:p.Ala9Val
LRG_288p2:p.Ala9Val
NC_000007.13:g.150674976G>A
NM_000238.2:c.26C>T
NM_000238.3:c.26C>T
NM_172056.2:c.26C>T
NR_176254.1:n.434C>T

Protein change:

A9V

Links:

dbSNP: rs775317201

NCBI 1000 Genomes Browser:

rs775317201

Molecular consequence:

NM_000238.4:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172056.3:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000234256	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Jan 7, 2019)	germline	clinical testing	Citation Link,
SCV000924812	Stanford Center for Inherited Cardiovascular Disease, Stanford University	no assertion criteria provided	Uncertain significance (Sep 12, 2016)	germline	provider interpretation

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000234256

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Jan 7, 2019)

germline

clinical testing

Citation Link,

SCV000924812

Stanford Center for Inherited Cardiovascular Disease, Stanford University

no assertion criteria provided

Uncertain significance
(Sep 12, 2016)

germline

provider interpretation

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	provider interpretation
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000234256.8

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

Description

The Ala9Val variant in the KCNH2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Ala9Val results in a conservative amino acid substitution of one non-polar amino acid with another at a position that is conserved across species. In silico analysis predicts Ala9Val is probably damaging to the protein structure/function. Mutations in nearby codons (Met1Leu, Asp16Ala) have been reported in association with LQTS, supporting the functional importance of this region of the protein. The NHLBI ESP Exome Variant Server reports Ala9Val was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations.With the clinical and molecular information available at this time, we cannot definitively determine if Ala9Val is a disease-causing 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 Stanford Center for Inherited Cardiovascular Disease, Stanford University, SCV000924812.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	provider interpretation	not provided

#	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: Oct 13, 2024

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