NM_000217.3(KCNA1):c.520G>A (p.Val174Ile) AND Episodic ataxia type 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 23, 2020
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:: RCV001232347.9

Allele description [Variation Report for NM_000217.3(KCNA1):c.520G>A (p.Val174Ile)]

NM_000217.3(KCNA1):c.520G>A (p.Val174Ile)

Gene:

KCNA1:potassium voltage-gated channel subfamily A member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.32

Genomic location:

Preferred name:

NM_000217.3(KCNA1):c.520G>A (p.Val174Ile)

HGVS:

NC_000012.12:g.4911898G>A
NG_011815.1:g.6992G>A
NM_000217.3:c.520G>AMANE SELECT
NP_000208.2:p.Val174Ile
LRG_1297t1:c.520G>A
LRG_1297:g.6992G>A
LRG_1297p1:p.Val174Ile
NC_000012.11:g.5021064G>A
NM_000217.2:c.520G>A

Protein change:

V174I

Links:

dbSNP: rs104894349

NCBI 1000 Genomes Browser:

rs104894349

Molecular consequence:

NM_000217.3:c.520G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Episodic ataxia type 1 (EA1)
Synonyms:: ATAXIA, EPISODIC, WITH MYOKYMIA; MYOKYMIA WITH PERIODIC ATAXIA; PAROXYSMAL ATAXIA WITH NEUROMYOTONIA, HEREDITARY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008047; MedGen: C1719788; Orphanet: 972; OMIM: 160120

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
SCV001404903	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 23, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 7842011, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001404903

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 23, 2020)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1.

Browne DL, Gancher ST, Nutt JG, Brunt ER, Smith EA, Kramer P, Litt M.

Nat Genet. 1994 Oct;8(2):136-40.

PubMed [citation]

PMID:: 7842011

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001404903.5

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Val174 amino acid residue in KCNA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7842011,¬†2245301, 8845167, 9526001 . This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has not been reported in the literature in individuals with KCNA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with isoleucine at codon 174 of the KCNA1 protein (p.Val174Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine