NM_001743.6(CALM2):c.328A>T (p.Met110Leu) AND Long QT syndrome 1

Clinical significance:Likely pathogenic (Last evaluated: Apr 17, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000544269.1

Allele description [Variation Report for NM_001743.6(CALM2):c.328A>T (p.Met110Leu)]

NM_001743.6(CALM2):c.328A>T (p.Met110Leu)

Gene:
CALM2:calmodulin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_001743.6(CALM2):c.328A>T (p.Met110Leu)
HGVS:
  • NC_000002.12:g.47161816T>A
  • NG_042065.1:g.20121A>T
  • NM_001305624.1:c.472A>T
  • NM_001305625.1:c.220A>T
  • NM_001305626.1:c.220A>T
  • NM_001743.6:c.328A>TMANE SELECT
  • NP_001292553.1:p.Met158Leu
  • NP_001292554.1:p.Met74Leu
  • NP_001292555.1:p.Met74Leu
  • NP_001734.1:p.Met110Leu
  • NC_000002.11:g.47388955T>A
  • NM_001743.4:c.328A>T
Protein change:
M110L
Links:
dbSNP: rs1553431711
NCBI 1000 Genomes Browser:
rs1553431711
Molecular consequence:
  • NM_001305624.1:c.472A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001305625.1:c.220A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001305626.1:c.220A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001743.6:c.328A>T - 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
SCV000629355Invitaecriteria provided, single submitter
Likely pathogenic
(Apr 17, 2017)
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, SCV000629355.1

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

Description

This sequence change replaces methionine with leucine at codon 110 of the CALM2 protein (p.Met110Leu). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and leucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CALM2-related disease. This variant has been shown to arise de novo in an individual affected with a CALM2-related condition (Invitae). 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. In summary, this variant is a novel missense change that arose de novo in an affected individual. This evidence indicates that the variant is pathogenic, but additional data is 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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