NM_000719.7(CACNA1C):c.5665C>T (p.Arg1889Cys) AND not provided

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Nov 17, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000171751.21

Allele description [Variation Report for NM_000719.7(CACNA1C):c.5665C>T (p.Arg1889Cys)]

NM_000719.7(CACNA1C):c.5665C>T (p.Arg1889Cys)

Genes:

CACNA1C-AS1:CACNA1C antisense RNA 1 [Gene - HGNC]
CACNA1C:calcium voltage-gated channel subunit alpha1 C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.33

Genomic location:

Preferred name:

NM_000719.7(CACNA1C):c.5665C>T (p.Arg1889Cys)

Other names:

p.R1889C:CGC>TGC

HGVS:

NC_000012.12:g.2685827C>T
NG_008801.2:g.720042C>T
NM_000719.7:c.5665C>TMANE SELECT
NM_001129827.2:c.5809C>T
NM_001129829.2:c.5788C>T
NM_001129830.3:c.5770C>T
NM_001129831.2:c.5749C>T
NM_001129832.2:c.5725C>T
NM_001129833.2:c.5722C>T
NM_001129834.2:c.5722C>T
NM_001129835.2:c.5722C>T
NM_001129836.2:c.5716C>T
NM_001129837.2:c.5689C>T
NM_001129838.2:c.5689C>T
NM_001129839.2:c.5683C>T
NM_001129840.2:c.5665C>T
NM_001129841.2:c.5665C>T
NM_001129842.2:c.5665C>T
NM_001129843.2:c.5665C>T
NM_001129844.2:c.5656C>T
NM_001129846.2:c.5632C>T
NM_001167623.2:c.5665C>T
NM_001167624.3:c.5770C>T
NM_001167625.2:c.5845C>T
NM_199460.4:c.5914C>T
NP_000710.5:p.Arg1889Cys
NP_001123299.1:p.Arg1937Cys
NP_001123301.1:p.Arg1930Cys
NP_001123302.2:p.Arg1924Cys
NP_001123303.1:p.Arg1917Cys
NP_001123304.1:p.Arg1909Cys
NP_001123305.1:p.Arg1908Cys
NP_001123306.1:p.Arg1908Cys
NP_001123307.1:p.Arg1908Cys
NP_001123308.1:p.Arg1906Cys
NP_001123309.1:p.Arg1897Cys
NP_001123310.1:p.Arg1897Cys
NP_001123311.1:p.Arg1895Cys
NP_001123312.1:p.Arg1889Cys
NP_001123313.1:p.Arg1889Cys
NP_001123314.1:p.Arg1889Cys
NP_001123315.1:p.Arg1889Cys
NP_001123316.1:p.Arg1886Cys
NP_001123318.1:p.Arg1878Cys
NP_001161095.1:p.Arg1889Cys
NP_001161096.2:p.Arg1924Cys
NP_001161097.1:p.Arg1949Cys
NP_955630.3:p.Arg1972Cys
LRG_334t1:c.5665C>T
LRG_334:g.720042C>T
LRG_334p1:p.Arg1889Cys
NC_000012.11:g.2794993C>T
NM_000719.6:c.5665C>T

Protein change:

R1878C

Links:

dbSNP: rs185788586

NCBI 1000 Genomes Browser:

rs185788586

Molecular consequence:

NM_000719.7:c.5665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129827.2:c.5809C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129829.2:c.5788C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129830.3:c.5770C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129831.2:c.5749C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129832.2:c.5725C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129833.2:c.5722C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129834.2:c.5722C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129835.2:c.5722C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129836.2:c.5716C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129837.2:c.5689C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129838.2:c.5689C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129839.2:c.5683C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129840.2:c.5665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129841.2:c.5665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129842.2:c.5665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129843.2:c.5665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129844.2:c.5656C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001129846.2:c.5632C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001167623.2:c.5665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001167624.3:c.5770C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001167625.2:c.5845C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_199460.4:c.5914C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000055189	Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013))	Likely benign (Jun 24, 2013)	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV000511587	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Feb 7, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000697554	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Jan 16, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23861362, 25661095, 25447171 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV001159344	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Benign (Nov 17, 2023)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	1	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Interpreting secondary cardiac disease variants in an exome cohort.

Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program..

Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16.

PubMed [citation]

PMID:: 23861362
PMCID:: PMC3887521

See all PubMed Citations (4)

Details of each submission

From Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq, SCV000055189.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV000511587.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	0.004664	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697554.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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.

#	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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001159344.4

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

#	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: Jun 9, 2024

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