NM_005413.4(SIX3):c.109G>T (p.Gly37Cys) AND Schizencephaly

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 1, 2010
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000023331.7

Allele description [Variation Report for NM_005413.4(SIX3):c.109G>T (p.Gly37Cys)]

NM_005413.4(SIX3):c.109G>T (p.Gly37Cys)

Gene:

SIX3:SIX homeobox 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_005413.4(SIX3):c.109G>T (p.Gly37Cys)

HGVS:

NC_000002.12:g.44942213G>T
NG_016222.1:g.5316G>T
NM_005413.4:c.109G>TMANE SELECT
NP_005404.1:p.Gly37Cys
NC_000002.11:g.45169352G>T
NM_005413.3:c.109G>T
O95343:p.Gly37Cys

Protein change:

G37C; GLY37CYS

Links:

UniProtKB: O95343#VAR_071335; OMIM: 603714.0009; dbSNP: rs199823175

NCBI 1000 Genomes Browser:

rs199823175

Molecular consequence:

NM_005413.4:c.109G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Schizencephaly
Identifiers:: MONDO: MONDO:0010011; MedGen: C0266484; Orphanet: 799; OMIM: 269160; Human Phenotype Ontology: HP:0010636

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000044622	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 2010)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 19346217, 18791198, 20157829

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000044622

OMIM

no assertion criteria provided

Pathogenic
(Mar 1, 2010)

germline

literature only

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function.

Lacbawan F, Solomon BD, Roessler E, El-Jaick K, Domené S, Vélez JI, Zhou N, Hadley D, Balog JZ, Long R, Fryer A, Smith W, Omar S, McLean SD, Clarkson K, Lichty A, Clegg NJ, Delgado MR, Levey E, Stashinko E, Potocki L, Vanallen MI, et al.

J Med Genet. 2009 Jun;46(6):389-98. doi: 10.1136/jmg.2008.063818. Epub 2009 Apr 2.

PubMed [citation]

PMID:: 19346217
PMCID:: PMC3510661

Mutations in the human SIX3 gene in holoprosencephaly are loss of function.

Domené S, Roessler E, El-Jaick KB, Snir M, Brown JL, Vélez JI, Bale S, Lacbawan F, Muenke M, Feldman B.

Hum Mol Genet. 2008 Dec 15;17(24):3919-28. doi: 10.1093/hmg/ddn294. Epub 2008 Sep 12.

PubMed [citation]

PMID:: 18791198
PMCID:: PMC2733808

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000044622.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

Holoprosencephaly 2

In 3 unrelated probands with variable manifestations of holoprosencephaly (HPE2; 157170), Lacbawan et al. (2009) identified a heterozygous 109G-T transversion in the SIX3 gene, resulting in a gly37-to-cys (G37C) substitution. One patient had unspecified HPE, 1 had lobar, and 1 had the middle interhemispheric variant; the unaffected mother of this last patient also carried the mutation. Functional studies in zebrafish by Domene et al. (2008) indicated that the G37C substitution was a hypomorphic allele.

Holoprosencephaly 2 and Schizencephaly

Hehr et al. (2010) identified a heterozygous G37C mutation in the SIX3 gene an 8-year-old girl with unilateral schizencephaly (269160) of the left hemisphere without evidence of HPE. She had normal intelligence, but slight spastic paresis of the right leg. Her father, paternal grandfather, and aunt also carried the mutation, and clinical examination of the father showed no evidence of HPE.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 12, 2024

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