NM_005198.4(CHKB):c.940C>T (p.Arg314Cys) AND Megaconial type congenital muscular dystrophy

Clinical significance:Uncertain significance (Last evaluated: Jan 12, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_005198.4(CHKB):c.940C>T (p.Arg314Cys)]

NM_005198.4(CHKB):c.940C>T (p.Arg314Cys)

CHKB-CPT1B:CHKB-CPT1B readthrough (NMD candidate) [Gene - HGNC]
CHKB:choline kinase beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_005198.4(CHKB):c.940C>T (p.Arg314Cys)
  • NC_000022.11:g.50579818G>A
  • NG_012643.1:g.3850C>T
  • NG_029213.1:g.8182C>T
  • NM_005198.4:c.940C>T
  • NP_005189.2:p.Arg314Cys
  • LRG_855t1:c.940C>T
  • LRG_855:g.8182C>T
  • LRG_855p1:p.Arg314Cys
  • NC_000022.10:g.51018247G>A
  • NR_027928.2:n.1158C>T
  • p.R314C
Protein change:
dbSNP: rs200919604
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_005198.4:c.940C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027928.2:n.1158C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]


Megaconial type congenital muscular dystrophy (MDCMC)
MONDO: MONDO:0011246; MedGen: C1865233; Orphanet: 280671; OMIM: 602541

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000439357Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Jan 12, 2018)
germlineclinical testing

Citation Link,

SCV000583509Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Geneticsno assertion criteria providedLikely pathogenic
(Oct 27, 2016)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
Muslim/Keralagermlineyes1not providednot providednot providednot providedclinical testing

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000439357.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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

From Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV000583509.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Muslim/Kerala1not providednot providedclinical testingnot provided


The observed mutation is not reported in 1000 Genomes and ExAC databases. The dbSNP reference number for the observed mutation is rs200919604. The in silico prediction of the mutation is damaging by SIFT and mutation Taster2 and benign by Polyphen2. The proband, born of consanguineous marriage, presented with clinical indications of Congenital muscular dystrophy. Further analysis revealed that he had a homozygous mutation c.940C>T (p.R314C) in exon 9 of CHKB gene. Both parents were found to be heterozygous for the same mutation. The DNA from amniotic fluid during subsequent pregnancy revealed a normal status of the fetus for the same mutation.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Apr 12, 2021

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