VCV000136622.14 - ClinVar

NM_000719.7(CACNA1C):c.3933C>T (p.Cys1311=)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign

3 out of 3 submissions contributed to this classification

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000719.7(CACNA1C):c.3933C>T (p.Cys1311=)

Variation ID: 136622 Accession: VCV000136622.14

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 12p13.33 12: 2648495 (GRCh38) [ NCBI UCSC ] 12: 2757661 (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	Jul 5, 2015	Feb 15, 2026	Dec 23, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000719.7:c.3933C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000710.5:p.Cys1311=	synonymous
NM_001167623.2:c.3933C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001161095.1:p.Cys1311=	synonymous
NM_001129827.2:c.4077C>T	NP_001123299.1:p.Cys1359=	synonymous
NM_001129829.2:c.3933C>T	NP_001123301.1:p.Cys1311=	synonymous
NM_001129830.3:c.3933C>T	NP_001123302.2:p.Cys1311=	synonymous
NM_001129831.2:c.4017C>T	NP_001123303.1:p.Cys1339=	synonymous
NM_001129832.2:c.3993C>T	NP_001123304.1:p.Cys1331=	synonymous
NM_001129833.2:c.3933C>T	NP_001123305.1:p.Cys1311=	synonymous
NM_001129834.2:c.3933C>T	NP_001123306.1:p.Cys1311=	synonymous
NM_001129835.2:c.3933C>T	NP_001123307.1:p.Cys1311=	synonymous
NM_001129836.2:c.3997-3145C>T		intron variant
NM_001129837.2:c.3913-3145C>T		intron variant
NM_001129838.2:c.3913-3145C>T		intron variant
NM_001129839.2:c.3907-3145C>T		intron variant
NM_001129840.2:c.3933C>T	NP_001123312.1:p.Cys1311=	synonymous
NM_001129841.2:c.3933C>T	NP_001123313.1:p.Cys1311=	synonymous
NM_001129842.2:c.3933C>T	NP_001123314.1:p.Cys1311=	synonymous
NM_001129843.2:c.3933C>T	NP_001123315.1:p.Cys1311=	synonymous
NM_001129844.2:c.3924C>T	NP_001123316.1:p.Cys1308=	synonymous
NM_001129846.2:c.3913-3145C>T		intron variant
NM_001167624.3:c.3933C>T	NP_001161096.2:p.Cys1311=	synonymous
NM_001167625.2:c.3913-3145C>T		intron variant
NM_199460.4:c.4077C>T	NP_955630.3:p.Cys1359=	synonymous
NC_000012.12:g.2648495C>T
NC_000012.11:g.2757661C>T
NG_008801.2:g.682710C>T
LRG_334:g.682710C>T
LRG_334t1:c.3933C>T

... more HGVS ... less HGVS

Protein change

Other names

p.C1311C:TGC>TGT

Canonical SPDI

NC_000012.12:2648494:C:T

Global minor allele frequency (GMAF) Help The 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.

0.00020 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.00005

The Genome Aggregation Database (gnomAD) 0.00007

The Genome Aggregation Database (gnomAD), exomes 0.00007

Exome Aggregation Consortium (ExAC) 0.00009

The Genome Aggregation Database (gnomAD), exomes 0.00009

1000 Genomes Project 30x 0.00016

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00016

1000 Genomes Project 0.00020

Links

ClinGen: CA289841 dbSNP: rs199569953 VarSome

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
Gene	OMIM	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	2634	3823

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.
not specified	Benign (1)	criteria provided, single submitter	Jul 10, 2011	RCV000124081.3
Long QT syndrome	Likely benign (1)	criteria provided, single submitter	Dec 23, 2025	RCV000559997.13
Cardiovascular phenotype	Likely benign (1)	criteria provided, single submitter	Dec 14, 2020	RCV002354312.2

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.	Expand all rows Collapse all rows 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 (Dec 23, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Long QT syndrome	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000627539.10 First in ClinVar: Dec 26, 2017 Last updated: Feb 15, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jul 10, 2011) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not specified	GeneDx Accession: SCV000167490.12 First in ClinVar: Jun 23, 2014 Last updated: Jul 05, 2015	Comment: show 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) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely benign (Dec 14, 2020) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV002621741.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: show This alteration is classified as likely 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) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

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 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.

Comment:

This alteration is classified as likely 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.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs199569953 ...

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 Feb 15, 2026