NM_001127222.2(CACNA1A):c.1810G>A (p.Val604Ile) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 1, 2023
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:: RCV001341763.10

Allele description [Variation Report for NM_001127222.2(CACNA1A):c.1810G>A (p.Val604Ile)]

NM_001127222.2(CACNA1A):c.1810G>A (p.Val604Ile)

Gene:

CACNA1A:calcium voltage-gated channel subunit alpha1 A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.13

Genomic location:

Preferred name:

NM_001127222.2(CACNA1A):c.1810G>A (p.Val604Ile)

HGVS:

NC_000019.10:g.13308223C>T
NG_011569.1:g.203238G>A
NM_000068.4:c.1813G>A
NM_001127221.2:c.1813G>A
NM_001127222.2:c.1810G>AMANE SELECT
NM_001174080.2:c.1813G>A
NM_023035.3:c.1813G>A
NP_000059.3:p.Val605Ile
NP_001120693.1:p.Val605Ile
NP_001120694.1:p.Val604Ile
NP_001167551.1:p.Val605Ile
NP_075461.2:p.Val605Ile
LRG_7t1:c.1813G>A
LRG_7:g.203238G>A
NC_000019.9:g.13419037C>T
NM_001127221.1:c.1813G>A

Protein change:

V604I

Links:

dbSNP: rs756562814

NCBI 1000 Genomes Browser:

rs756562814

Molecular consequence:

NM_000068.4:c.1813G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127221.2:c.1813G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127222.2:c.1810G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001174080.2:c.1813G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_023035.3:c.1813G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Episodic ataxia type 2 (EA2)
Synonyms:: Episodic ataxia with nystagmus; Nystagmus-associated episodic ataxia; Cerebellopathy, hereditary paroxysmal; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007163; MedGen: C1720416; Orphanet: 97; OMIM: 108500

Name:: Developmental and epileptic encephalopathy, 42 (DEE42)
Synonyms:: Epileptic encephalopathy, early infantile, 42
Identifiers:: MONDO: MONDO:0014917; MedGen: C4310716; OMIM: 617106

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
SCV001535654	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 1, 2023)	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

SCV001535654

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 1, 2023)

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, SCV001535654.5

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

Description

Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CACNA1A protein function. ClinVar contains an entry for this variant (Variation ID: 808479). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. This variant is present in population databases (rs756562814, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 605 of the CACNA1A protein (p.Val605Ile). 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.

#	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 8, 2024

ClinVar

Relating variation to medicine