NM_024665.7(TBL1XR1):c.1108G>A (p.Asp370Asn) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Sep 1, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000412858.12

Allele description

NM_024665.7(TBL1XR1):c.1108G>A (p.Asp370Asn)

Genes:

LOC126806878:CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:176755168-176756367 [Gene]
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.1108G>A (p.Asp370Asn)

HGVS:

NC_000003.12:g.177038112C>T
NG_047195.1:g.164149G>A
NM_001321193.3:c.1108G>A
NM_001321194.3:c.1108G>A
NM_001321195.3:c.847G>A
NM_001374327.1:c.1108G>A
NM_001374328.1:c.1108G>A
NM_001374329.1:c.1108G>A
NM_001374330.1:c.847G>A
NM_024665.7:c.1108G>AMANE SELECT
NP_001308122.1:p.Asp370Asn
NP_001308123.1:p.Asp370Asn
NP_001308124.1:p.Asp283Asn
NP_001361256.1:p.Asp370Asn
NP_001361257.1:p.Asp370Asn
NP_001361258.1:p.Asp370Asn
NP_001361259.1:p.Asp283Asn
NP_078941.2:p.Asp370Asn
NC_000003.11:g.176755900C>T
NM_024665.4:c.1108G>A
NM_024665.6:c.1108G>A

Protein change:

D283N

Links:

dbSNP: rs1057517933

NCBI 1000 Genomes Browser:

rs1057517933

Molecular consequence:

NM_001321193.3:c.1108G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001321194.3:c.1108G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001321195.3:c.847G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374327.1:c.1108G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374328.1:c.1108G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374329.1:c.1108G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374330.1:c.847G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024665.7:c.1108G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000491102	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (May 1, 2017)	germline	clinical testing	Citation Link,
SCV002586004	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (Sep 1, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000491102

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(May 1, 2017)

germline

clinical testing

Citation Link,

SCV002586004

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely pathogenic
(Sep 1, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000491102.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The D370N pathogenic variant in the TBL1XR1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The D370N variant was not observed in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D370N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue (D370Y) has been reported in a nonverbal female with global developmental delay (Laskowski et al., 2016), supporting the functional importance of this region of the protein. We interpret D370N as a pathogenic variant.

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

From CeGaT Center for Human Genetics Tuebingen, SCV002586004.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

TBL1XR1: PM2, PM5, PP2, PP3, PS4:Supporting

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

Last Updated: May 12, 2024

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