NM_001743.6(CALM2):c.396T>G (p.Asp132Glu) AND Long QT syndrome 15

Clinical significance:Pathogenic (Last evaluated: Aug 20, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000162069.5

Allele description [Variation Report for NM_001743.6(CALM2):c.396T>G (p.Asp132Glu)]

NM_001743.6(CALM2):c.396T>G (p.Asp132Glu)

Gene:
CALM2:calmodulin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_001743.6(CALM2):c.396T>G (p.Asp132Glu)
HGVS:
  • NC_000002.12:g.47161748A>C
  • NG_042065.1:g.20189T>G
  • NM_001305624.1:c.540T>G
  • NM_001305625.1:c.288T>G
  • NM_001305626.1:c.288T>G
  • NM_001743.6:c.396T>GMANE SELECT
  • NP_001292553.1:p.Asp180Glu
  • NP_001292554.1:p.Asp96Glu
  • NP_001292555.1:p.Asp96Glu
  • NP_001734.1:p.Asp132Glu
  • NC_000002.11:g.47388887A>C
  • NM_001743.4:c.396T>G
  • P62158:p.Asp132Glu
  • p.D132E
Protein change:
D132E; ASP132GLU
Links:
UniProtKB: P62158#VAR_073279; OMIM: 114182.0005; dbSNP: rs398124648
NCBI 1000 Genomes Browser:
rs398124648
Molecular consequence:
  • NM_001305624.1:c.540T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001305625.1:c.288T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001305626.1:c.288T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001743.6:c.396T>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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
SCV000212102OMIMno assertion criteria providedPathogenic
(Aug 1, 2014)
germlineliterature only

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

SCV001150036Institute of Human Genetics, Klinikum rechts der Isarcriteria provided, single submitter
Pathogenic
(Aug 20, 2018)
de novoclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedde novoyes1not providednot provided1not providedclinical testing
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

Details of each submission

From OMIM, SCV000212102.2

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

Description

In a 29-year-old German woman with perinatal bradycardia and neonatal long QT syndrome (LQT15; 616249), who later exhibited exercise-induced polymorphic ventricular ectopy, Makita et al. (2014) identified heterozygosity for a de novo c.396T-G transversion in the CALM2 gene, resulting in an asp132-to-glu (D132E) substitution at a conserved residue within the fourth EF-hand calcium-binding motif. The mutation was not found in her parents or in the dbSNP, 1000 Genomes Project, Exome Variant Server, or Helmholtz exome databases. Functional analysis demonstrated a 23-fold reduction in calcium-binding affinity with the D132E mutant compared to wildtype calmodulin.

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

From Institute of Human Genetics, Klinikum rechts der Isar, SCV001150036.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyes1bloodnot provided1not providednot providednot provided

Last Updated: Oct 16, 2021

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