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NM_000069.3(CACNA1S):c.3795G>T (p.Gln1265His)

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Interpretation:
Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
3 (Most recent: Aug 10, 2021)
Last evaluated:
May 21, 2021
Accession:
VCV000633684.4
Variation ID:
633684
Description:
single nucleotide variant
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NM_000069.3(CACNA1S):c.3795G>T (p.Gln1265His)

Allele ID
622090
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1q32.1
Genomic location
1: 201053459 (GRCh38) GRCh38 UCSC
1: 201022587 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.10:g.201022587C>A
NC_000001.11:g.201053459C>A
NG_009816.1:g.64108G>T
... more HGVS
Protein change
Q1265H
Other names
-
Canonical SPDI
NC_000001.11:201053458:C:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
dbSNP: rs201627041
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 2 criteria provided, single submitter May 21, 2021 RCV000782249.3
Likely pathogenic 1 criteria provided, single submitter Jun 22, 2020 RCV001377927.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CACNA1S No evidence available No evidence available GRCh38
GRCh37
1121 1136

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Jun 22, 2020)
criteria provided, single submitter
Method: clinical testing
Hypokalemic periodic paralysis 1
Malignant hyperthermia, susceptibility to, 5
Allele origin: germline
Invitae
Accession: SCV001575382.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces glutamine with histidine at codon 1265 of the CACNA1S protein (p.Gln1265His). The glutamine residue is highly conserved and there is a … (more)
Likely pathogenic
(May 21, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001779251.1
Submitted: (Aug 10, 2021)
Evidence details
Comment:
Reported in a patient with hypokalemic periodic paralysis (Al-Ghamdi et al., 2017); Not observed at a significant frequency in large population cohorts (Lek et al., … (more)
Uncertain significance
(Sep 16, 2018)
no assertion criteria provided
Method: research
not provided
Allele origin: germline
Gharavi Laboratory,Columbia University
Accession: SCV000920739.1
Submitted: (Mar 05, 2019)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy. Schartner V Acta neuropathologica 2017 PMID: 28012042
Novel pathogenic variants and genes for myopathies identified by whole exome sequencing. Hunter JM Molecular genetics & genomic medicine 2015 PMID: 26247046
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. Buratti E Nucleic acids research 2007 PMID: 17576681
Statistical features of human exons and their flanking regions. Zhang MQ Human molecular genetics 1998 PMID: 9536098

Text-mined citations for rs201627041...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 23, 2021