ClinVar Genomic variation as it relates to human health
NM_000719.7(CACNA1C):c.109G>A (p.Gly37Arg)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000719.7(CACNA1C):c.109G>A (p.Gly37Arg)
Variation ID: 93391 Accession: VCV000093391.43
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 12p13.33 12: 2115283 (GRCh38) [ NCBI UCSC ] 12: 2224449 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jun 8, 2015 Sep 29, 2024 Jan 31, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000719.7:c.109G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000710.5:p.Gly37Arg missense NM_001167623.2:c.109G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001161095.1:p.Gly37Arg missense NM_001129827.2:c.109G>A NP_001123299.1:p.Gly37Arg missense NM_001129829.2:c.109G>A NP_001123301.1:p.Gly37Arg missense NM_001129830.3:c.109G>A NP_001123302.2:p.Gly37Arg missense NM_001129831.2:c.109G>A NP_001123303.1:p.Gly37Arg missense NM_001129832.2:c.109G>A NP_001123304.1:p.Gly37Arg missense NM_001129833.2:c.109G>A NP_001123305.1:p.Gly37Arg missense NM_001129834.2:c.109G>A NP_001123306.1:p.Gly37Arg missense NM_001129835.2:c.109G>A NP_001123307.1:p.Gly37Arg missense NM_001129836.2:c.109G>A NP_001123308.1:p.Gly37Arg missense NM_001129837.2:c.109G>A NP_001123309.1:p.Gly37Arg missense NM_001129838.2:c.109G>A NP_001123310.1:p.Gly37Arg missense NM_001129839.2:c.109G>A NP_001123311.1:p.Gly37Arg missense NM_001129840.2:c.109G>A NP_001123312.1:p.Gly37Arg missense NM_001129841.2:c.109G>A NP_001123313.1:p.Gly37Arg missense NM_001129842.2:c.109G>A NP_001123314.1:p.Gly37Arg missense NM_001129843.2:c.109G>A NP_001123315.1:p.Gly37Arg missense NM_001129844.2:c.109G>A NP_001123316.1:p.Gly37Arg missense NM_001129846.2:c.109G>A NP_001123318.1:p.Gly37Arg missense NM_001167624.3:c.109G>A NP_001161096.2:p.Gly37Arg missense NM_001167625.2:c.109G>A NP_001161097.1:p.Gly37Arg missense NM_199460.4:c.109G>A NP_955630.3:p.Gly37Arg missense NC_000012.12:g.2115283G>A NC_000012.11:g.2224449G>A NG_008801.2:g.149498G>A LRG_334:g.149498G>A LRG_334t1:c.109G>A LRG_334p1:p.Gly37Arg - Protein change
- G37R
- Other names
- -
- Canonical SPDI
- NC_000012.12:2115282:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00040 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00031
1000 Genomes Project 0.00040
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00232
Trans-Omics for Precision Medicine (TOPMed) 0.00251
The Genome Aggregation Database (gnomAD) 0.00346
The Genome Aggregation Database (gnomAD), exomes 0.00346
Exome Aggregation Consortium (ExAC) 0.00738
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
CACNA1C | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
2086 | 3047 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Nov 1, 2023 | RCV000079275.34 | |
Likely benign (4) |
criteria provided, single submitter
|
Jul 16, 2014 | RCV000173030.15 | |
Benign (1) |
criteria provided, single submitter
|
May 28, 2019 | RCV000306251.11 | |
Benign (1) |
criteria provided, single submitter
|
Sep 4, 2015 | RCV000622244.10 | |
Benign (1) |
criteria provided, single submitter
|
Jan 31, 2024 | RCV001082290.16 | |
Likely benign (1) |
criteria provided, single submitter
|
Apr 11, 2022 | RCV002498393.8 | |
CACNA1C-related disorder
|
Likely benign (1) |
criteria provided, single submitter
|
Sep 9, 2019 | RCV003944997.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Likely benign
(Jun 24, 2013)
|
criteria provided, single submitter
Method: research
|
Not provided
Affected status: unknown
Allele origin:
unknown
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000050756.1 First in ClinVar: Jun 08, 2015 Last updated: Jun 08, 2015
Comments (2):
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less)
Medical sequencing
|
Number of individuals with the variant: 1
|
|
Benign
(Nov 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001890790.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 26498160)
|
|
Likely benign
(Apr 11, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Timothy syndrome
Brugada syndrome 3 Long qt syndrome 8
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002809049.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Benign
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Long QT syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000218722.12
First in ClinVar: Mar 29, 2015 Last updated: Feb 20, 2024 |
|
|
Benign
(Sep 04, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000735199.4
First in ClinVar: Apr 14, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
Likely benign
(Nov 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV003916801.11
First in ClinVar: Apr 23, 2023 Last updated: Aug 04, 2024 |
Comment:
CACNA1C: PP2, PP3, BS1, BS2
Number of individuals with the variant: 4
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005213023.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
Likely benign
(Jul 16, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000111145.8
First in ClinVar: Jan 23, 2014 Last updated: Jun 28, 2015 |
Number of individuals with the variant: 3
Sex: mixed
|
|
Benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Timothy syndrome
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001138622.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
Likely benign
(Oct 10, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002049935.2
First in ClinVar: Jan 08, 2022 Last updated: Feb 20, 2024 |
|
|
Likely benign
(Sep 09, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
CACNA1C-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004774048.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001919553.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927830.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001954118.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
click to load more click to collapse |
Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CACNA1C | - | - | - | - |
Text-mined citations for rs34534613 ...
HelpRecord last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.