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NM_001195553.2(DCX):c.190T>G (p.Tyr64Asp) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 3, 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:
RCV003685084.2

Allele description [Variation Report for NM_001195553.2(DCX):c.190T>G (p.Tyr64Asp)]

NM_001195553.2(DCX):c.190T>G (p.Tyr64Asp)

Gene:
DCX:doublecortin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq23
Genomic location:
Preferred name:
NM_001195553.2(DCX):c.190T>G (p.Tyr64Asp)
HGVS:
  • NC_000023.11:g.111410209A>C
  • NG_011750.1:g.6970T>G
  • NM_000555.3:c.433T>G
  • NM_001195553.2:c.190T>GMANE SELECT
  • NM_001369370.1:c.190T>G
  • NM_001369371.1:c.190T>G
  • NM_001369372.1:c.190T>G
  • NM_001369373.1:c.190T>G
  • NM_001369374.1:c.190T>G
  • NM_001410715.1:c.190T>G
  • NM_178151.3:c.190T>G
  • NM_178152.3:c.190T>G
  • NM_178153.3:c.190T>G
  • NP_000546.2:p.Tyr145Asp
  • NP_001182482.1:p.Tyr64Asp
  • NP_001356299.1:p.Tyr64Asp
  • NP_001356300.1:p.Tyr64Asp
  • NP_001356301.1:p.Tyr64Asp
  • NP_001356302.1:p.Tyr64Asp
  • NP_001356303.1:p.Tyr64Asp
  • NP_001397644.1:p.Tyr64Asp
  • NP_835364.1:p.Tyr64Asp
  • NP_835365.1:p.Tyr64Asp
  • NP_835366.1:p.Tyr64Asp
  • NC_000023.10:g.110653437A>C
Protein change:
Y145D
Molecular consequence:
  • NM_000555.3:c.433T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195553.2:c.190T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369370.1:c.190T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369371.1:c.190T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369372.1:c.190T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369373.1:c.190T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369374.1:c.190T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001410715.1:c.190T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_178151.3:c.190T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_178152.3:c.190T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_178153.3:c.190T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004406906Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 3, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

The location of DCX mutations predicts malformation severity in X-linked lissencephaly.

Leger PL, Souville I, Boddaert N, Elie C, Pinard JM, Plouin P, Moutard ML, des Portes V, Van Esch H, Joriot S, Renard JL, Chelly J, Francis F, Beldjord C, Bahi-Buisson N.

Neurogenetics. 2008 Oct;9(4):277-85. doi: 10.1007/s10048-008-0141-5. Epub 2008 Aug 7.

PubMed [citation]
PMID:
18685874

Comprehensive genomic analysis of patients with disorders of cerebral cortical development.

Wiszniewski W, Gawlinski P, Gambin T, Bekiesinska-Figatowska M, Obersztyn E, Antczak-Marach D, Akdemir ZHC, Harel T, Karaca E, Jurek M, Sobecka K, Nowakowska B, Kruk M, Terczynska I, Goszczanska-Ciuchta A, Rudzka-Dybala M, Jamroz E, Pyrkosz A, Jakubiuk-Tomaszuk A, Iwanowski P, Gieruszczak-Bialek D, Piotrowicz M, et al.

Eur J Hum Genet. 2018 Aug;26(8):1121-1131. doi: 10.1038/s41431-018-0137-z. Epub 2018 Apr 30.

PubMed [citation]
PMID:
29706646
PMCID:
PMC6057976
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004406906.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Tyr64 amino acid residue in DCX. Other variant(s) that disrupt this residue have been observed in individuals with DCX-related conditions (PMID: 18685874, 29706646; Invitae), which suggests that this may be a clinically significant amino acid residue. 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 DCX protein function. This missense change has been observed in individual(s) with lissencephaly (Invitae). 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 tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 64 of the DCX protein (p.Tyr64Asp).

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

Last Updated: Sep 29, 2024