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

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Sep 25, 2021)
Last evaluated:
Sep 10, 2020
Accession:
VCV000143823.4
Variation ID:
143823
Description:
single nucleotide variant
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NM_001323289.2(CDKL5):c.532C>T (p.Arg178Trp)

Allele ID
153555
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
Xp22.13
Genomic location
X: 18584331 (GRCh38) GRCh38 UCSC
X: 18602451 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000023.10:g.18602451C>T
NC_000023.11:g.18584331C>T
NG_008475.1:g.163727C>T
... more HGVS
Protein change
R178W
Other names
p.R178W:CGG>TGG
Canonical SPDI
NC_000023.11:18584330:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
RettBASE (CDKL5): 69
ClinGen: CA199283
dbSNP: rs267608493
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, single submitter Dec 26, 2019 RCV000133373.6
Pathogenic 2 criteria provided, single submitter Nov 1, 2016 RCV000169986.2
Pathogenic 1 criteria provided, single submitter May 16, 2017 RCV000544362.1
Pathogenic 1 criteria provided, single submitter Sep 10, 2020 RCV001260657.1
Likely pathogenic 1 no assertion criteria provided May 15, 2014 RCV000169915.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CDKL5 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
766 1270

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Dec 26, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000190958.11
Submitted: (Sep 25, 2021)
Evidence details
Comment:
Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This … (more)
Pathogenic
(May 16, 2017)
criteria provided, single submitter
Method: clinical testing
Early infantile epileptic encephalopathy 2
Angelman syndrome-like
Allele origin: germline
Invitae
Accession: SCV000639479.1
Submitted: (Oct 05, 2017)
Evidence details
Comment:
This sequence change replaces arginine with tryptophan at codon 178 of the CDKL5 protein (p.Arg178Trp). The arginine residue is highly conserved and there is a … (more)
Pathogenic
(Nov 01, 2016)
criteria provided, single submitter
Method: clinical testing
Atypical Rett syndrome
Allele origin: germline
Center for Human Genetics, Inc,Center for Human Genetics, Inc
Accession: SCV000781090.1
Submitted: (Dec 20, 2017)
Evidence details
Pathogenic
(Sep 10, 2020)
criteria provided, single submitter
Method: clinical testing
Intellectual disability
Allele origin: de novo
Diagnostic Laboratory, Strasbourg University Hospital
Accession: SCV001437749.1
Submitted: (Sep 18, 2020)
Evidence details
Likely pathogenic
(May 15, 2014)
no assertion criteria provided
Method: curation
Epileptic encephalopathy, early infantile, 2
Allele origin: de novo
RettBASE
Accession: SCV000188387.2
Submitted: (Nov 21, 2014)
Evidence details
Comment:
In silico prediction: SIFT = deleterious, MutationTaster = disease-causing, PolyPhen2 = probably damaging, AlignGVGD = benign (C0)
Likely pathogenic
(May 15, 2014)
no assertion criteria provided
Method: curation
Atypical Rett syndrome
Allele origin: unknown
RettBASE
Accession: SCV000222291.1
Submitted: (Nov 21, 2014)
Evidence details
Comment:
In silico prediction: SIFT = deleterious, MutationTaster = disease-causing, PolyPhen2 = probably damaging, AlignGVGD = benign (C0)
Pathogenic
(Feb 13, 2015)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia
Accession: SCV000256045.1
Submitted: (Mar 20, 2015)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Variant of Rett syndrome and CDKL5 gene: clinical and autonomic description of 10 cases. Pini G Neuropediatrics 2012 PMID: 22430159
Mutational spectrum of CDKL5 in early-onset encephalopathies: a study of a large collection of French patients and review of the literature. Nemos C Clinical genetics 2009 PMID: 19793311

Text-mined citations for rs267608493...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Dec 04, 2021