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NM_001323289.2(CDKL5):c.532C>T (p.Arg178Trp) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 6, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:

Allele description [Variation Report for NM_001323289.2(CDKL5):c.532C>T (p.Arg178Trp)]

NM_001323289.2(CDKL5):c.532C>T (p.Arg178Trp)

CDKL5:cyclin dependent kinase like 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001323289.2(CDKL5):c.532C>T (p.Arg178Trp)
Other names:
  • NC_000023.11:g.18584331C>T
  • NG_008475.1:g.163727C>T
  • NM_001037343.2:c.532C>T
  • NM_001323289.2:c.532C>TMANE SELECT
  • NM_003159.3:c.532C>T
  • NP_001032420.1:p.Arg178Trp
  • NP_001310218.1:p.Arg178Trp
  • NP_003150.1:p.Arg178Trp
  • NP_003150.1:p.Arg178Trp
  • NC_000023.10:g.18602451C>T
  • NM_003159.2:c.532C>T
  • p.(Arg178Trp)
Protein change:
RettBASE (CDKL5): 69; dbSNP: rs267608493
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001037343.2:c.532C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323289.2:c.532C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003159.3:c.532C>T - missense variant - [Sequence Ontology: SO:0001583]


Inborn genetic diseases
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV002646833Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
(Jun 6, 2019)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy.

Elia M, Falco M, Ferri R, Spalletta A, Bottitta M, Calabrese G, Carotenuto M, Musumeci SA, Lo Giudice M, Fichera M.

Neurology. 2008 Sep 23;71(13):997-9. doi: 10.1212/01.wnl.0000326592.37105.88.

PubMed [citation]

Early-onset seizure variant of Rett syndrome: definition of the clinical diagnostic criteria.

Artuso R, Mencarelli MA, Polli R, Sartori S, Ariani F, Pollazzon M, Marozza A, Cilio MR, Specchio N, Vigevano F, Vecchi M, Boniver C, Dalla Bernardina B, Parmeggiani A, Buoni S, Hayek G, Mari F, Renieri A, Murgia A.

Brain Dev. 2010 Jan;32(1):17-24. doi: 10.1016/j.braindev.2009.02.004. Epub 2009 Apr 10.

PubMed [citation]
See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV002646833.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)


The p.R178W pathogenic mutation (also known as c.532C>T), located in coding exon 7 of the CDKL5 gene, results from a C to T substitution at nucleotide position 532. The arginine at codon 178 is replaced by tryptophan, an amino acid with dissimilar properties. This pathogenic mutation has been reported in multiple individuals with severe epileptic encephalopathy and/or Rett-syndrome like features (Artuso R et al. Brain Dev., 2010 Jan;32:17-24; Pini G et al. Neuropediatrics, 2012 Feb;43:37-43; Bahi-Buisson N et al. Am. J. Med. Genet. A, 2012 Jul;158A:1612-9), including in some cases as a confirmed de novo occurrence (Nemos C et al. Clin. Genet., 2009 Oct;76:357-71; Hamdan FF et al. Am. J. Hum. Genet., 2017 Nov;101:664-685). In addition, disease-causing alterations at the same codon have previously been reported, including p.R178P (Elia M et al. Neurology, 2008 Sep;71:997-9; Nemos C et al. Clin. Genet., 2009 Oct;76:357-71; Bahi-Buisson N et al. Am. J. Med. Genet. A, 2012 Jul;158A:1612-9), p.R178Q (Liang JS et al. Epilepsia, 2011 Oct;52:1835-42; Bahi-Buisson N et al. Am. J. Med. Genet. A, 2012 Jul;158A:1612-9), and p.R178L (Miao P et al. Clin. Genet., 2018 Dec;94:512-520). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Jun 23, 2024