NM_006888.6(CALM1):c.161A>T (p.Asn54Ile) AND Catecholaminergic polymorphic ventricular tachycardia 4

Germline classification:: Likely pathogenic (4 submissions)
Last evaluated:: Jul 22, 2020
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:: RCV000032976.41

Allele description [Variation Report for NM_006888.6(CALM1):c.161A>T (p.Asn54Ile)]

NM_006888.6(CALM1):c.161A>T (p.Asn54Ile)

Gene:

CALM1:calmodulin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q32.11

Genomic location:

Preferred name:

NM_006888.6(CALM1):c.161A>T (p.Asn54Ile)

Other names:

N53I

HGVS:

NC_000014.9:g.90401385A>T
NG_013338.1:g.9403A>T
NM_001363669.2:c.53A>T
NM_001363670.2:c.164A>T
NM_006888.6:c.161A>TMANE SELECT
NP_001350598.1:p.Asn18Ile
NP_001350599.1:p.Asn55Ile
NP_008819.1:p.Asn54Ile
NP_008819.1:p.Asn54Ile
NC_000014.8:g.90867729A>T
NM_006888.4:c.161A>T
NP_008819.1:p.Asn53Ile
P62158:p.Asn54Ile

Note:

NCBI staff reviewed the sequence information reported in PubMed 23040497 to determine the location of this allele on the current reference sequence. Their numbering of Asn53Ile, if begun at Met1, will be Asn54Ile.

Protein change:

N18I; ASN53ILE

Links:

UniProtKB: P62158#VAR_069222; OMIM: 114180.0001; dbSNP: rs267607276

NCBI 1000 Genomes Browser:

rs267607276

Molecular consequence:

NM_001363669.2:c.53A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363670.2:c.164A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006888.6:c.161A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Catecholaminergic polymorphic ventricular tachycardia 4
Identifiers:: MONDO: MONDO:0013966; MedGen: C3554047; Orphanet: 3286; OMIM: 614916

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000056751	OMIM	no assertion criteria provided	Pathogenic (Oct 5, 2012)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000147939	GeneReviews	no classification provided	not provided	germline	literature only
SCV000187713	Nyegaard lab; Aarhus University	no assertion criteria provided	Pathogenic (Jul 23, 2012)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV001426215	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 22, 2020)	unknown	curation	PubMed (5) [See all records that cite these PMIDs] 23040497, 23388215, 26164367, 27165696, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	10	1	not provided	not provided	yes	literature only, research
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death.

Nyegaard M, Overgaard MT, Søndergaard MT, Vranas M, Behr ER, Hildebrandt LL, Lund J, Hedley PL, Camm AJ, Wettrell G, Fosdal I, Christiansen M, Børglum AD.

Am J Hum Genet. 2012 Oct 5;91(4):703-12. doi: 10.1016/j.ajhg.2012.08.015.

PubMed [citation]

PMID:: 23040497
PMCID:: PMC3484646

Calmodulin mutations associated with recurrent cardiac arrest in infants.

Crotti L, Johnson CN, Graf E, De Ferrari GM, Cuneo BF, Ovadia M, Papagiannis J, Feldkamp MD, Rathi SG, Kunic JD, Pedrazzini M, Wieland T, Lichtner P, Beckmann BM, Clark T, Shaffer C, Benson DW, Kääb S, Meitinger T, Strom TM, Chazin WJ, Schwartz PJ, et al.

Circulation. 2013 Mar 5;127(9):1009-17. doi: 10.1161/CIRCULATIONAHA.112.001216. Epub 2013 Feb 6.

PubMed [citation]

PMID:: 23388215
PMCID:: PMC3834768

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000056751.1

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

Description

In 10 affected members of a large 4-generation Swedish family with catecholaminergic polymorphic ventricular tachycardia (CPVT4; 614916), Nyegaard et al. (2012) identified heterozygosity for a 161A-T transversion in exon 3 of the CALM1 gene, resulting in an asn53-to-ile (N53I) substitution at a highly conserved residue within the first alpha-helix of Ca(2+)-binding site II. The mutation was not found in unaffected family members or in 1,200 controls. Functional analysis demonstrated that the mutant had significantly reduced Ca(2+) affinity compared to wildtype.

#	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	not provided	not provided	not provided

From GeneReviews, SCV000147939.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	not provided

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

From Nyegaard lab; Aarhus University, SCV000187713.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	10	not provided	yes	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	discovery		10	not provided	1	not provided

From SIB Swiss Institute of Bioinformatics, SCV001426215.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (5)

Description

This variant is interpreted as likely pathogenic for Ventricular tachycardia, catecholaminergic polymorphic, 4, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1 upgraded to moderate); Well-established functional studies show a deleterious effect (PS3 downgraded to moderate).

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 1, 2024

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