NM_001323289.2(CDKL5):c.1891A>G (p.Ile631Val) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 6, 2023
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:
RCV000689153.7

Allele description [Variation Report for NM_001323289.2(CDKL5):c.1891A>G (p.Ile631Val)]

NM_001323289.2(CDKL5):c.1891A>G (p.Ile631Val)

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.1891A>G (p.Ile631Val)
HGVS:
  • NC_000023.11:g.18604815A>G
  • NG_008475.1:g.184211A>G
  • NM_001037343.2:c.1891A>G
  • NM_001323289.2:c.1891A>GMANE SELECT
  • NM_003159.3:c.1891A>G
  • NP_001032420.1:p.Ile631Val
  • NP_001310218.1:p.Ile631Val
  • NP_003150.1:p.Ile631Val
  • NP_003150.1:p.Ile631Val
  • NC_000023.10:g.18622935A>G
  • NM_003159.2:c.1891A>G
Protein change:
I631V
Links:
dbSNP: rs1569219817
NCBI 1000 Genomes Browser:
rs1569219817
Molecular consequence:
  • NM_001037343.2:c.1891A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323289.2:c.1891A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003159.3:c.1891A>G - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000816793Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 6, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000816793.4

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

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 631 of the CDKL5 protein (p.Ile631Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDKL5-related conditions. ClinVar contains an entry for this variant (Variation ID: 568711). 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 not expected to disrupt CDKL5 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024