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NM_001195553.2(DCX):c.665C>T (p.Thr222Ile) AND Lissencephaly type 1 due to doublecortin gene mutation

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 15, 2018
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:
RCV000984506.2

Allele description [Variation Report for NM_001195553.2(DCX):c.665C>T (p.Thr222Ile)]

NM_001195553.2(DCX):c.665C>T (p.Thr222Ile)

Gene:
DCX:doublecortin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq23
Genomic location:
Preferred name:
NM_001195553.2(DCX):c.665C>T (p.Thr222Ile)
HGVS:
  • NC_000023.11:g.111401030G>A
  • NG_011750.1:g.16149C>T
  • NM_000555.3:c.908C>T
  • NM_001195553.2:c.665C>TMANE SELECT
  • NM_001369370.1:c.665C>T
  • NM_001369371.1:c.665C>T
  • NM_001369372.1:c.665C>T
  • NM_001369373.1:c.665C>T
  • NM_001369374.1:c.665C>T
  • NM_178151.3:c.665C>T
  • NM_178152.3:c.665C>T
  • NM_178153.3:c.665C>T
  • NP_000546.2:p.Thr303Ile
  • NP_001182482.1:p.Thr222Ile
  • NP_001356299.1:p.Thr222Ile
  • NP_001356300.1:p.Thr222Ile
  • NP_001356301.1:p.Thr222Ile
  • NP_001356302.1:p.Thr222Ile
  • NP_001356303.1:p.Thr222Ile
  • NP_835364.1:p.Thr222Ile
  • NP_835365.1:p.Thr222Ile
  • NP_835366.1:p.Thr222Ile
  • NC_000023.10:g.110644258G>A
  • p.Thr303Ile
Protein change:
T222I
Links:
dbSNP: rs1603423268
NCBI 1000 Genomes Browser:
rs1603423268
Molecular consequence:
  • NM_000555.3:c.908C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195553.2:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369370.1:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369371.1:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369372.1:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369373.1:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369374.1:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_178151.3:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_178152.3:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_178153.3:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Lissencephaly type 1 due to doublecortin gene mutation
Synonyms:
LISSENCEPHALY, X-LINKED, 1; Lissencephaly and agenesis of corpus callosum
Identifiers:
MONDO: MONDO:0010239; MedGen: C4551968; Orphanet: 2148; OMIM: 300067

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001132562Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Nov 15, 2018) 		de novoresearch

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedde novoyesnot providednot providednot providednot providednot providedresearch

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001132562.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)

Description

The hemizygous p.Thr303Ile variant in DCX was identified by our study in one individual with Lissencephaly. Trio exome analysis showed this variant to be de novo. This variant was absent from large population studies. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 26, 2024