NM_000702.4(ATP1A2):c.1709C>T (p.Thr570Met) AND Familial hemiplegic migraine

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 16, 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:: RCV001323714.7

Allele description [Variation Report for NM_000702.4(ATP1A2):c.1709C>T (p.Thr570Met)]

NM_000702.4(ATP1A2):c.1709C>T (p.Thr570Met)

Gene:

ATP1A2:ATPase Na+/K+ transporting subunit alpha 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q23.2

Genomic location:

Preferred name:

NM_000702.4(ATP1A2):c.1709C>T (p.Thr570Met)

HGVS:

NC_000001.11:g.160130479C>T
NG_008014.1:g.19722C>T
NM_000702.4:c.1709C>TMANE SELECT
NP_000693.1:p.Thr570Met
LRG_6:g.19722C>T
NC_000001.10:g.160100269C>T

Protein change:

T570M

Links:

dbSNP: rs758815329

NCBI 1000 Genomes Browser:

rs758815329

Molecular consequence:

NM_000702.4:c.1709C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial hemiplegic migraine
Identifiers:: MONDO: MONDO:0000700; MedGen: C0338484; OMIM: PS141500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001514642	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 16, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27066515, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001514642

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 16, 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

Next-generation sequencing identifies novel CACNA1A gene mutations in episodic ataxia type 2.

Maksemous N, Roy B, Smith RA, Griffiths LR.

Mol Genet Genomic Med. 2016 Mar;4(2):211-22. doi: 10.1002/mgg3.196.

PubMed [citation]

PMID:: 27066515
PMCID:: PMC4799871

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, SCV001514642.4

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

Description

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: "Benign"; Align-GVGD: "Class C65"). This variant has been observed in individual(s) with clinical features of episodic ataxia (PMID: 27066515). This variant is present in population databases (rs758815329, ExAC 0.03%). This sequence change replaces threonine with methionine at codon 570 of the ATP1A2 protein (p.Thr570Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine.

#	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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