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NM_001323289.2(CDKL5):c.58G>C (p.Gly20Arg) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 19, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002515935.2

Allele description [Variation Report for NM_001323289.2(CDKL5):c.58G>C (p.Gly20Arg)]

NM_001323289.2(CDKL5):c.58G>C (p.Gly20Arg)

Gene:
CDKL5:cyclin dependent kinase like 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp22.13
Genomic location:
Preferred name:
NM_001323289.2(CDKL5):c.58G>C (p.Gly20Arg)
HGVS:
  • NC_000023.11:g.18507154G>C
  • NG_008475.1:g.86550G>C
  • NM_001037343.2:c.58G>C
  • NM_001323289.2:c.58G>CMANE SELECT
  • NM_003159.3:c.58G>C
  • NP_001032420.1:p.Gly20Arg
  • NP_001310218.1:p.Gly20Arg
  • NP_003150.1:p.Gly20Arg
  • NP_003150.1:p.Gly20Arg
  • NC_000023.10:g.18525274G>C
  • NM_003159.2:c.58G>C
Protein change:
G20R
Links:
RettBASE (CDKL5): 93; dbSNP: rs267608418
NCBI 1000 Genomes Browser:
rs267608418
Molecular consequence:
  • NM_001037343.2:c.58G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323289.2:c.58G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003159.3:c.58G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Developmental and epileptic encephalopathy, 2 (DEE2)
Synonyms:
INFANTILE SPASM SYNDROME, X-LINKED 2; Early infantile epileptic encephalopathy 2
Identifiers:
MONDO: MONDO:0010396; MedGen: C4750718; Orphanet: 1934; Orphanet: 3451; OMIM: 300672
Name:
Angelman syndrome-like
Identifiers:
MedGen: CN128785

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003444503Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Aug 19, 2022)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Cyclin-dependent kinase-like 5 (CDKL5) mutation screening in Rett syndrome and related disorders.

White R, Ho G, Schmidt S, Scheffer IE, Fischer A, Yendle SC, Bienvenu T, Nectoux J, Ellaway CJ, Darmanian A, Tong X, Cloosterman D, Bennetts B, Kalra V, Fullston T, Gecz J, Cox TC, Christodoulou J.

Twin Res Hum Genet. 2010 Apr;13(2):168-78. doi: 10.1375/twin.13.2.168.

PubMed [citation]
PMID:
20397747

Gene mutational analysis in a cohort of Chinese children with unexplained epilepsy: Identification of a new KCND3 phenotype and novel genes causing Dravet syndrome.

Wang J, Wen Y, Zhang Q, Yu S, Chen Y, Wu X, Zhang Y, Bao X.

Seizure. 2019 Mar;66:26-30. doi: 10.1016/j.seizure.2019.01.025. Epub 2019 Jan 28.

PubMed [citation]
PMID:
30776697
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003444503.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CDKL5 protein function. ClinVar contains an entry for this variant (Variation ID: 143828). This missense change has been observed in individual(s) with CDKL5-related conditions (PMID: 20397747, 30776697). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 20 of the CDKL5 protein (p.Gly20Arg).

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

Last Updated: Feb 28, 2024