NM_207037.2(TCF12):c.1876C>T (p.Arg626Ter) AND not provided

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

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Nov 1, 2023
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:: RCV001861454.15

Allele description

NM_207037.2(TCF12):c.1876C>T (p.Arg626Ter)

Gene:

TCF12:transcription factor 12 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q21.3

Genomic location:

Preferred name:

NM_207037.2(TCF12):c.1876C>T (p.Arg626Ter)

HGVS:

NC_000015.10:g.57273160C>T
NG_033851.2:g.360071C>T
NM_001306219.3:c.1366C>T
NM_001306220.3:c.1096C>T
NM_001322151.2:c.1876C>T
NM_001322152.2:c.1873C>T
NM_001322154.2:c.1219C>T
NM_001322156.2:c.1702C>T
NM_001322157.3:c.1804C>T
NM_001322158.2:c.1630C>T
NM_001322159.3:c.1876C>T
NM_001322161.2:c.1873C>T
NM_001322162.2:c.1876C>T
NM_001322164.2:c.1840C>T
NM_001322165.2:c.1804C>T
NM_003205.4:c.1804C>T
NM_207036.2:c.1876C>T
NM_207037.2:c.1876C>TMANE SELECT
NM_207038.2:c.1804C>T
NM_207040.2:c.1294C>T
NP_001293148.1:p.Arg456Ter
NP_001293149.1:p.Arg366Ter
NP_001309080.1:p.Arg626Ter
NP_001309081.1:p.Arg625Ter
NP_001309083.1:p.Arg407Ter
NP_001309085.1:p.Arg568Ter
NP_001309086.1:p.Arg602Ter
NP_001309087.1:p.Arg544Ter
NP_001309088.1:p.Arg626Ter
NP_001309090.1:p.Arg625Ter
NP_001309091.1:p.Arg626Ter
NP_001309093.1:p.Arg614Ter
NP_001309094.1:p.Arg602Ter
NP_003196.1:p.Arg602Ter
NP_996919.1:p.Arg626Ter
NP_996920.1:p.Arg626Ter
NP_996921.1:p.Arg602Ter
NP_996923.1:p.Arg432Ter
NC_000015.9:g.57565358C>T
NM_207036.1:c.1876C>T

Protein change:

R366*

Links:

dbSNP: rs758543580

NCBI 1000 Genomes Browser:

rs758543580

Molecular consequence:

NM_001306219.3:c.1366C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001306220.3:c.1096C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322151.2:c.1876C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322152.2:c.1873C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322154.2:c.1219C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322156.2:c.1702C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322157.3:c.1804C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322158.2:c.1630C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322159.3:c.1876C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322161.2:c.1873C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322162.2:c.1876C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322164.2:c.1840C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322165.2:c.1804C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_003205.4:c.1804C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_207036.2:c.1876C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_207037.2:c.1876C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_207038.2:c.1804C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_207040.2:c.1294C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002228818	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 20, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 29215649, 23354436, 32620954, 28492532
SCV002502634	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 2, 2021)	de novo	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29215649, 25741868
SCV002549206	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jul 7, 2022)	germline	clinical testing	Citation Link,
SCV004184467	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Nov 1, 2023)	germline	clinical testing	Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.

Sharma VP, Fenwick AL, Brockop MS, McGowan SJ, Goos JA, Hoogeboom AJ, Brady AF, Jeelani NO, Lynch SA, Mulliken JB, Murray DJ, Phipps JM, Sweeney E, Tomkins SE, Wilson LC, Bennett S, Cornall RJ, Broxholme J, Kanapin A; 500 Whole-Genome Sequences (WGS500) Consortium., Johnson D, Wall SA, et al.

Nat Genet. 2013 Mar;45(3):304-7. doi: 10.1038/ng.2531. Epub 2013 Jan 27. Erratum in: Nat Genet. 2013 Oct;45(10):1261.

PubMed [citation]

PMID:: 23354436
PMCID:: PMC3647333

TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.

Davis EE, Balasubramanian R, Kupchinsky ZA, Keefe DL, Plummer L, Khan K, Meczekalski B, Heath KE, Lopez-Gonzalez V, Ballesta-Martinez MJ, Margabanthu G, Price S, Greening J, Brauner R, Valenzuela I, Cusco I, Fernandez-Alvarez P, Wierman ME, Li T, Lage K, Barroso PS, Chan YM, et al.

Hum Mol Genet. 2020 Aug 11;29(14):2435-2450. doi: 10.1093/hmg/ddaa120.

PubMed [citation]

PMID:: 32620954
PMCID:: PMC7608740

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002228818.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 374377). This premature translational stop signal has been observed in individual(s) with craniosynostosis (PMID: 29215649). This variant is present in population databases (rs758543580, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg626*) in the TCF12 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TCF12 are known to be pathogenic (PMID: 23354436, 32620954).

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

From AiLife Diagnostics, AiLife Diagnostics, SCV002502634.1

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

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

From GeneDx, SCV002549206.2

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29215649, 33004838)

#	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, SCV004184467.8

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

Description

TCF12: PVS1, PM2, 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: Oct 8, 2024

ClinVar

Relating variation to medicine