NM_024665.7(TBL1XR1):c.734A>G (p.Tyr245Cys) AND Intellectual disability, autosomal dominant 41

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 19, 2022
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:: RCV000211092.4

Allele description [Variation Report for NM_024665.7(TBL1XR1):c.734A>G (p.Tyr245Cys)]

NM_024665.7(TBL1XR1):c.734A>G (p.Tyr245Cys)

Genes:

TBL1XR1:TBL1X/Y related 1 [Gene - OMIM - HGNC]
TBL1XR1-AS1:TBL1XR1 antisense RNA 1 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q26.32

Genomic location:

Preferred name:

NM_024665.7(TBL1XR1):c.734A>G (p.Tyr245Cys)

HGVS:

NC_000003.12:g.177047518T>C
NG_047195.1:g.154743A>G
NM_001321193.3:c.734A>G
NM_001321194.3:c.734A>G
NM_001321195.3:c.473A>G
NM_001374327.1:c.734A>G
NM_001374328.1:c.734A>G
NM_001374329.1:c.734A>G
NM_001374330.1:c.473A>G
NM_024665.7:c.734A>GMANE SELECT
NP_001308122.1:p.Tyr245Cys
NP_001308123.1:p.Tyr245Cys
NP_001308124.1:p.Tyr158Cys
NP_001361256.1:p.Tyr245Cys
NP_001361257.1:p.Tyr245Cys
NP_001361258.1:p.Tyr245Cys
NP_001361259.1:p.Tyr158Cys
NP_078941.2:p.Tyr245Cys
NC_000003.11:g.176765306T>C
NM_024665.4:c.734A>G
NM_024665.5:c.734A>G
Q9BZK7:p.Tyr245Cys

Protein change:

Y158C; TYR245CYS

Links:

UniProtKB: Q9BZK7#VAR_076755; OMIM: 608628.0004; dbSNP: rs878854401

NCBI 1000 Genomes Browser:

rs878854401

Molecular consequence:

NM_001321193.3:c.734A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001321194.3:c.734A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001321195.3:c.473A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374327.1:c.734A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374328.1:c.734A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374329.1:c.734A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374330.1:c.473A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024665.7:c.734A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Intellectual disability, autosomal dominant 41 (MRD41)
Synonyms:: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 41
Identifiers:: MONDO: MONDO:0014842; MedGen: C4310784; Orphanet: 2823; OMIM: 616944

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000268060	OMIM	no assertion criteria provided	Pathogenic (Jul 19, 2022)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 27133561, 19760657

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000268060

OMIM

no assertion criteria provided

Pathogenic
(Jul 19, 2022)

germline

literature only

PubMed (2)
[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

Syndrome disintegration: Exome sequencing reveals that Fitzsimmons syndrome is a co-occurrence of multiple events.

Armour CM, Smith A, Hartley T, Chardon JW, Sawyer S, Schwartzentruber J, Hennekam R, Majewski J, Bulman DE; FORGE Canada Consortium., Suri M, Boycott KM.

Am J Med Genet A. 2016 Jul;170(7):1820-5. doi: 10.1002/ajmg.a.37684. Epub 2016 May 2.

PubMed [citation]

PMID:: 27133561

Fitzsimmons syndrome: spastic paraplegia, brachydactyly and cognitive impairment.

Armour CM, Humphreys P, Hennekam RC, Boycott KM.

Am J Med Genet A. 2009 Oct;149A(10):2254-7. doi: 10.1002/ajmg.a.33003.

PubMed [citation]

PMID:: 19760657

Details of each submission

From OMIM, SCV000268060.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a patient with autosomal dominant intellectual developmental disorder-41 (MRD41; 616944), Armour et al. (2016) identified a de novo heterozygous c.734A-G transition in the TBL1XR1 gene, resulting in a tyr245-to-cys (Y245C) substitution at a highly conserved residue. The mutation was found by exome sequencing and confirmed by Sanger sequencing. The patient was originally reported by Armour et al. (2009) as having spastic paraparesis, brachydactyly, and dysmorphic facial features, but Armour et al. (2016) concluded that these additional features may not have been caused by the TBL1XR1 mutation. Functional studies of the variant were not performed.

#	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: Oct 8, 2024

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