ClinVar Genomic variation as it relates to human health
NM_000719.7(CACNA1C):c.5665C>T (p.Arg1889Cys)
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.5665C>T (p.Arg1889Cys)
Variation ID: 93417 Accession: VCV000093417.34
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 12p13.33 12: 2685827 (GRCh38) [ NCBI UCSC ] 12: 2794993 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 May 1, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000719.7:c.5665C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000710.5:p.Arg1889Cys missense NM_001167623.2:c.5665C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001161095.1:p.Arg1889Cys missense NM_001129827.2:c.5809C>T NP_001123299.1:p.Arg1937Cys missense NM_001129829.2:c.5788C>T NP_001123301.1:p.Arg1930Cys missense NM_001129830.3:c.5770C>T NP_001123302.2:p.Arg1924Cys missense NM_001129831.2:c.5749C>T NP_001123303.1:p.Arg1917Cys missense NM_001129832.2:c.5725C>T NP_001123304.1:p.Arg1909Cys missense NM_001129833.2:c.5722C>T NP_001123305.1:p.Arg1908Cys missense NM_001129834.2:c.5722C>T NP_001123306.1:p.Arg1908Cys missense NM_001129835.2:c.5722C>T NP_001123307.1:p.Arg1908Cys missense NM_001129836.2:c.5716C>T NP_001123308.1:p.Arg1906Cys missense NM_001129837.2:c.5689C>T NP_001123309.1:p.Arg1897Cys missense NM_001129838.2:c.5689C>T NP_001123310.1:p.Arg1897Cys missense NM_001129839.2:c.5683C>T NP_001123311.1:p.Arg1895Cys missense NM_001129840.2:c.5665C>T NP_001123312.1:p.Arg1889Cys missense NM_001129841.2:c.5665C>T NP_001123313.1:p.Arg1889Cys missense NM_001129842.2:c.5665C>T NP_001123314.1:p.Arg1889Cys missense NM_001129843.2:c.5665C>T NP_001123315.1:p.Arg1889Cys missense NM_001129844.2:c.5656C>T NP_001123316.1:p.Arg1886Cys missense NM_001129846.2:c.5632C>T NP_001123318.1:p.Arg1878Cys missense NM_001167624.3:c.5770C>T NP_001161096.2:p.Arg1924Cys missense NM_001167625.2:c.5845C>T NP_001161097.1:p.Arg1949Cys missense NM_199460.4:c.5914C>T NP_955630.3:p.Arg1972Cys missense NC_000012.12:g.2685827C>T NC_000012.11:g.2794993C>T NG_008801.2:g.720042C>T LRG_334:g.720042C>T LRG_334t1:c.5665C>T LRG_334p1:p.Arg1889Cys - Protein change
- R1889C, R1924C, R1937C, R1949C, R1897C, R1886C, R1895C, R1906C, R1930C, R1908C, R1917C, R1878C, R1909C, R1972C
- Other names
- p.R1889C:CGC>TGC
- Canonical SPDI
- NC_000012.12:2685826:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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0.00859 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00138
The Genome Aggregation Database (gnomAD) 0.00182
Trans-Omics for Precision Medicine (TOPMed) 0.00441
Exome Aggregation Consortium (ExAC) 0.00749
1000 Genomes Project 0.00859
1000 Genomes Project 30x 0.00906
The Genome Aggregation Database (gnomAD), exomes 0.01020
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 | ||
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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. |
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CACNA1C | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
2059 | 3011 | |
CACNA1C-AS1 | - | - | - |
GRCh38 GRCh38 |
- | 836 |
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. |
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Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Jul 14, 2015 | RCV000079302.31 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Nov 17, 2023 | RCV000171751.21 | |
Benign (1) |
criteria provided, single submitter
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Jun 23, 2020 | RCV002272059.9 | |
Benign (1) |
criteria provided, single submitter
|
Sep 4, 2015 | RCV000621082.11 | |
Likely benign (1) |
criteria provided, single submitter
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Aug 16, 2017 | RCV000852666.9 | |
Benign (1) |
criteria provided, single submitter
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Feb 1, 2024 | RCV001079466.15 |
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. |
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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: SCV000055189.1 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
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Number of individuals with the variant: 1
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Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000305456.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
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Benign
(Feb 07, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000511587.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
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Benign
(Jan 16, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697554.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
Variant summary: The CACNA1C c.5665C>T (p.Arg1889Cys) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant … (more)
Variant summary: The CACNA1C c.5665C>T (p.Arg1889Cys) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 899/121392 control chromosomes (36 homozygotes), predominantly observed in the Latino subpopulation at a frequency of 0.0728206 (837/11494). This frequency is about 7282 times the estimated maximal expected allele frequency of a pathogenic CACNA1C variant (0.00001), strong evidence that this is a benign polymorphism found primarily in the populations of Latino origin. The variant has been reported in the literature, without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. (less)
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Benign
(Jul 14, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000332653.3
First in ClinVar: Dec 06, 2016 Last updated: May 03, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
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Likely benign
(Aug 16, 2017)
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criteria provided, single submitter
Method: clinical testing
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Arrhythmogenic right ventricular cardiomyopathy
Affected status: yes
Allele origin:
germline
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Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego
Accession: SCV000995373.1
First in ClinVar: Oct 12, 2019 Last updated: Oct 12, 2019 |
Number of individuals with the variant: 1
|
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Benign
(Jun 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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Timothy syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556950.2
First in ClinVar: Aug 08, 2022 Last updated: Dec 17, 2022 |
Comment:
The CACNA1C c.5665C>T variant is classified as Benign (BA1, BP4) The frequency of this variant in population databases is higher than expected for this disorder … (more)
The CACNA1C c.5665C>T variant is classified as Benign (BA1, BP4) The frequency of this variant in population databases is higher than expected for this disorder indicating this variant is a benign polymorphism (BA1). Multiple lines of computational evidence suggest this variant has no impact on the gene or gene product (BP4). The variant has been reported in dbSNP (rs185788586) and in the HGMD database: CM1413436 - ?disease causing mutation. It has been reported as Benign/Likely benign by other diagnostic laboratories (ClinVar Variation ID: 93417). (less)
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Long QT syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000260703.11
First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024 |
|
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Benign
(Sep 04, 2015)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000735502.4
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)
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Likely benign
(Sep 07, 2011)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000167512.12
First in ClinVar: Jun 23, 2014 Last updated: Apr 03, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Nov 17, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001159344.4
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001923047.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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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: SCV001953297.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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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 |
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Next generation sequencing for molecular confirmation of hereditary sudden cardiac death syndromes. | Márquez MF | Archivos de cardiologia de Mexico | 2015 | PMID: 25661095 |
Post-mortem genetic analysis in juvenile cases of sudden cardiac death. | Campuzano O | Forensic science international | 2014 | PMID: 25447171 |
Interpreting secondary cardiac disease variants in an exome cohort. | Ng D | Circulation. Cardiovascular genetics | 2013 | PMID: 23861362 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CACNA1C | - | - | - | - |
Text-mined citations for rs185788586 ...
HelpRecord last updated May 19, 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.