NM_000719.7(CACNA1C):c.5735G>A (p.Gly1912Glu) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 10, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001215035.7

Allele description [Variation Report for NM_000719.7(CACNA1C):c.5735G>A (p.Gly1912Glu)]

NM_000719.7(CACNA1C):c.5735G>A (p.Gly1912Glu)

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.5735G>A (p.Gly1912Glu)

HGVS:

NC_000012.12:g.2686220G>A
NG_008801.2:g.720435G>A
NM_000719.7:c.5735G>AMANE SELECT
NM_001129827.2:c.5879G>A
NM_001129829.2:c.5858G>A
NM_001129830.3:c.5840G>A
NM_001129831.2:c.5819G>A
NM_001129832.2:c.5795G>A
NM_001129833.2:c.5792G>A
NM_001129834.2:c.5792G>A
NM_001129835.2:c.5792G>A
NM_001129836.2:c.5786G>A
NM_001129837.2:c.5759G>A
NM_001129838.2:c.5759G>A
NM_001129839.2:c.5753G>A
NM_001129840.2:c.5735G>A
NM_001129841.2:c.5735G>A
NM_001129842.2:c.5735G>A
NM_001129843.2:c.5735G>A
NM_001129844.2:c.5726G>A
NM_001129846.2:c.5702G>A
NM_001167623.2:c.5735G>A
NM_001167624.3:c.5840G>A
NM_001167625.2:c.5915G>A
NM_199460.4:c.5984G>A
NP_000710.5:p.Gly1912Glu
NP_001123299.1:p.Gly1960Glu
NP_001123301.1:p.Gly1953Glu
NP_001123302.2:p.Gly1947Glu
NP_001123303.1:p.Gly1940Glu
NP_001123304.1:p.Gly1932Glu
NP_001123305.1:p.Gly1931Glu
NP_001123306.1:p.Gly1931Glu
NP_001123307.1:p.Gly1931Glu
NP_001123308.1:p.Gly1929Glu
NP_001123309.1:p.Gly1920Glu
NP_001123310.1:p.Gly1920Glu
NP_001123311.1:p.Gly1918Glu
NP_001123312.1:p.Gly1912Glu
NP_001123313.1:p.Gly1912Glu
NP_001123314.1:p.Gly1912Glu
NP_001123315.1:p.Gly1912Glu
NP_001123316.1:p.Gly1909Glu
NP_001123318.1:p.Gly1901Glu
NP_001161095.1:p.Gly1912Glu
NP_001161096.2:p.Gly1947Glu
NP_001161097.1:p.Gly1972Glu
NP_955630.3:p.Gly1995Glu
LRG_334t1:c.5735G>A
LRG_334:g.720435G>A
NC_000012.11:g.2795386G>A
NM_000719.6:c.5735G>A

Protein change:

G1901E

Links:

dbSNP: rs2097476034

NCBI 1000 Genomes Browser:

rs2097476034

Molecular consequence:

NM_000719.7:c.5735G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129827.2:c.5879G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129829.2:c.5858G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129830.3:c.5840G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129831.2:c.5819G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129832.2:c.5795G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129833.2:c.5792G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129834.2:c.5792G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129835.2:c.5792G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129836.2:c.5786G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129837.2:c.5759G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129838.2:c.5759G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129839.2:c.5753G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129840.2:c.5735G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129841.2:c.5735G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129842.2:c.5735G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129843.2:c.5735G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129844.2:c.5726G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001129846.2:c.5702G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001167623.2:c.5735G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001167624.3:c.5840G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001167625.2:c.5915G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_199460.4:c.5984G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Long QT syndrome (LQTS)
Identifiers:: MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001386754	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 10, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001386754

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 10, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001386754.5

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

Description

This sequence change replaces glycine with glutamic acid at codon 1912 of the CACNA1C protein (p.Gly1912Glu). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CACNA1C-related conditions. This variant is not present in population databases (ExAC no frequency).

#	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: Sep 29, 2024

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