NM_021098.3(CACNA1H):c.2491G>A (p.Val831Met) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 28, 2022
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:: RCV001321101.7

Allele description [Variation Report for NM_021098.3(CACNA1H):c.2491G>A (p.Val831Met)]

NM_021098.3(CACNA1H):c.2491G>A (p.Val831Met)

Gene:

CACNA1H:calcium voltage-gated channel subunit alpha1 H [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_021098.3(CACNA1H):c.2491G>A (p.Val831Met)

HGVS:

NC_000016.10:g.1205153G>A
NG_012647.1:g.56913G>A
NM_001005407.2:c.2491G>A
NM_021098.3:c.2491G>AMANE SELECT
NP_001005407.1:p.Val831Met
NP_066921.2:p.Val831Met
NC_000016.9:g.1255153G>A
O95180:p.Val831Met

Protein change:

V831M; VAL831MET

Links:

UniProtKB: O95180#VAR_045950; OMIM: 607904.0003; dbSNP: rs119454949

NCBI 1000 Genomes Browser:

rs119454949

Molecular consequence:

NM_001005407.2:c.2491G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021098.3:c.2491G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Idiopathic generalized epilepsy
Synonyms:: EIG; Generalised epilepsy
Identifiers:: MONDO: MONDO:0005579; MedGen: C0270850; OMIM: 600669; OMIM: PS600669

Name:: Hyperaldosteronism, familial, type IV (HALD4)
Synonyms:: FH IV; ALDOSTERONISM, PRIMARY, AND HYPERTENSION
Identifiers:: MONDO: MONDO:0014875; MedGen: C4310756; OMIM: 617027

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001511916	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 28, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 14729682, 15888660, 12891677, 31130284, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001511916

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 28, 2022)

germline

clinical testing

PubMed (5)
[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

Gating effects of mutations in the Cav3.2 T-type calcium channel associated with childhood absence epilepsy.

Khosravani H, Altier C, Simms B, Hamming KS, Snutch TP, Mezeyova J, McRory JE, Zamponi GW.

J Biol Chem. 2004 Mar 12;279(11):9681-4. Epub 2004 Jan 16.

PubMed [citation]

PMID:: 14729682

Functional characterization and neuronal modeling of the effects of childhood absence epilepsy variants of CACNA1H, a T-type calcium channel.

Vitko I, Chen Y, Arias JM, Shen Y, Wu XR, Perez-Reyes E.

J Neurosci. 2005 May 11;25(19):4844-55.

PubMed [citation]

PMID:: 15888660
PMCID:: PMC6724770

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001511916.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

ClinVar contains an entry for this variant (Variation ID: 2703). 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. Experimental studies have shown that this missense change affects CACNA1H function (PMID: 14729682, 15888660). 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) performed at Invitae indicates that this missense variant is expected to disrupt CACNA1H protein function. This missense change has been observed in individual(s) with clinical features of CACNA1H-related conditions (PMID: 12891677, 31130284). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 831 of the CACNA1H protein (p.Val831Met).

#	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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