NM_000217.3(KCNA1):c.1046C>A (p.Ala349Glu) AND Episodic ataxia type 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 15, 2021
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:: RCV001921215.4

Allele description [Variation Report for NM_000217.3(KCNA1):c.1046C>A (p.Ala349Glu)]

NM_000217.3(KCNA1):c.1046C>A (p.Ala349Glu)

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.1046C>A (p.Ala349Glu)

HGVS:

NC_000012.12:g.4912424C>A
NG_011815.1:g.7518C>A
NM_000217.3:c.1046C>AMANE SELECT
NP_000208.2:p.Ala349Glu
LRG_1297t1:c.1046C>A
LRG_1297:g.7518C>A
LRG_1297p1:p.Ala349Glu
NC_000012.11:g.5021590C>A

Protein change:

A349E

Links:

dbSNP: rs1361446640

NCBI 1000 Genomes Browser:

rs1361446640

Molecular consequence:

NM_000217.3:c.1046C>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

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COX3 [Harpegnathos venator]
COX3 [Harpegnathos venator]
Gene ID:86134153

Gene
Danio rerio strain Tuebingen chromosome 21, GRCz11 Primary Assembly
Danio rerio strain Tuebingen chromosome 21, GRCz11 Primary Assembly
gi|1196813932|gnl|ASM:GCF_000000175 ef|NC_007132.7||gpp|GPC_000003040.1||gnl|NCBI_GENOMES|709

Nucleotide
popset representative uid 166952443[word] (168)
Nucleotide
BioProject Links for Protein (Select 604723372) (2)
BioProject
membrane protein ycf1, partial (chloroplast) [Astragalus viridis]
membrane protein ycf1, partial (chloroplast) [Astragalus viridis]
gi|815860479|gb|AKE49167.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002189388	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002189388

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 15, 2021)

germline

clinical testing

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

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

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, SCV002189388.3

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

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with glutamic acid at codon 349 of the KCNA1 protein (p.Ala349Glu). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant has not been reported in the literature in individuals affected with KCNA1-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15").

#	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

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