NM_001743.6(CALM2):c.293A>G (p.Asn98Ser) AND Long QT syndrome 15

Clinical significance:Pathogenic (Last evaluated: Aug 1, 2014)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000162067.4

Allele description [Variation Report for NM_001743.6(CALM2):c.293A>G (p.Asn98Ser)]

NM_001743.6(CALM2):c.293A>G (p.Asn98Ser)

Gene:
CALM2:calmodulin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_001743.6(CALM2):c.293A>G (p.Asn98Ser)
HGVS:
  • NC_000002.12:g.47161851T>C
  • NG_042065.1:g.20086A>G
  • NM_001305624.1:c.437A>G
  • NM_001305625.1:c.185A>G
  • NM_001305626.1:c.185A>G
  • NM_001743.6:c.293A>GMANE SELECT
  • NP_001292553.1:p.Asn146Ser
  • NP_001292554.1:p.Asn62Ser
  • NP_001292555.1:p.Asn62Ser
  • NP_001734.1:p.Asn98Ser
  • NC_000002.11:g.47388990T>C
  • NM_001743.4:c.293A>G
  • P62158:p.Asn98Ser
  • p.N98S
Protein change:
N146S; ASN98SER
Links:
UniProtKB: P62158#VAR_069223; OMIM: 114182.0003; dbSNP: rs398124647
NCBI 1000 Genomes Browser:
rs398124647
Molecular consequence:
  • NM_001305624.1:c.437A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001305625.1:c.185A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001305626.1:c.185A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001743.6:c.293A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome 15 (LQT15)
Identifiers:
MONDO: MONDO:0014550; MedGen: C4015695; Orphanet: 101016; Orphanet: 768; OMIM: 616249

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000212100OMIMno assertion criteria providedPathogenic
(Aug 1, 2014)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Novel calmodulin mutations associated with congenital arrhythmia susceptibility.

Makita N, Yagihara N, Crotti L, Johnson CN, Beckmann BM, Roh MS, Shigemizu D, Lichtner P, Ishikawa T, Aiba T, Homfray T, Behr ER, Klug D, Denjoy I, Mastantuono E, Theisen D, Tsunoda T, Satake W, Toda T, Nakagawa H, Tsuji Y, Tsuchiya T, et al.

Circ Cardiovasc Genet. 2014 Aug;7(4):466-74. doi: 10.1161/CIRCGENETICS.113.000459. Epub 2014 Jun 10.

PubMed [citation]
PMID:
24917665
PMCID:
PMC4140998

Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A103V) Activates Arrhythmogenic Ca Waves and Sparks.

Gomez-Hurtado N, Boczek NJ, Kryshtal DO, Johnson CN, Sun J, Nitu FR, Cornea RL, Chazin WJ, Calvert ML, Tester DJ, Ackerman MJ, Knollmann BC.

Circ Arrhythm Electrophysiol. 2016 Aug;9(8). doi:pii: e004161. 10.1161/CIRCEP.116.004161.

PubMed [citation]
PMID:
27516456
PMCID:
PMC4988333

Details of each submission

From OMIM, SCV000212100.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a 12-year-old Japanese boy with episodes of syncope on exertion and QTc prolongation on electrocardiography (LQT15; 616249), Makita et al. (2014) identified heterozygosity for a de novo c.293A-G transition in exon 5 of the CALM2 gene, resulting in an asn98-to-ser (N98S) substitution at a conserved residue within the third EF-hand calcium-binding motif in the C-terminal domain. The mutation was not found in his unaffected parents or brother.

Gomez-Hurtado et al. (2016) studied the CALM2 N98S mutation in permeabilized mouse ventricular myocytes and observed significantly increased spark frequency and reduced sarcoplasmic reticulum Ca(2+) content with the mutant compared to wildtype calmodulin. The cardiomyocytes also showed increased spontaneous Ca(2+) release in the form of regular propagated Ca(2+) waves with the mutant compared to wildtype calmodulin, and the mutant demonstrated a dominant effect, with significantly higher Ca(2+) wave frequencies even in the presence of 3-fold excess of wildtype calmodulin.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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