NM_001743.6(CALM2):c.434T>G (p.Met145Arg) AND Long QT syndrome 1

Clinical significance:Likely pathogenic (Last evaluated: Jun 12, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000698791.1

Allele description [Variation Report for NM_001743.6(CALM2):c.434T>G (p.Met145Arg)]

NM_001743.6(CALM2):c.434T>G (p.Met145Arg)

Gene:
CALM2:calmodulin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_001743.6(CALM2):c.434T>G (p.Met145Arg)
HGVS:
  • NC_000002.12:g.47160792A>C
  • NG_042065.1:g.21145T>G
  • NM_001305624.1:c.578T>G
  • NM_001305625.1:c.326T>G
  • NM_001305626.1:c.326T>G
  • NM_001743.6:c.434T>GMANE SELECT
  • NP_001292553.1:p.Met193Arg
  • NP_001292554.1:p.Met109Arg
  • NP_001292555.1:p.Met109Arg
  • NP_001734.1:p.Met145Arg
  • NC_000002.11:g.47387931A>C
  • NM_001743.4:c.434T>G
Protein change:
M109R
Links:
dbSNP: rs1558693760
NCBI 1000 Genomes Browser:
rs1558693760
Molecular consequence:
  • NM_001305624.1:c.578T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001305625.1:c.326T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001305626.1:c.326T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001743.6:c.434T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome 1 (LQT1)
Identifiers:
MONDO: MONDO:0100316; MedGen: C4551647; Orphanet: 101016; Orphanet: 768; OMIM: 192500

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000827477Invitaecriteria provided, single submitter
Likely pathogenic
(Jun 12, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000827477.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces methionine with arginine at codon 145 of the CALM2 protein (p.Met145Arg). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in individuals affected with CALM2-related clinical features (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 7, 2021

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