NM_000474.4(TWIST1):c.211C>T (p.Gln71Ter) AND TWIST1-related craniosynostosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 1, 2022
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:: RCV002283441.1

Allele description [Variation Report for NM_000474.4(TWIST1):c.211C>T (p.Gln71Ter)]

NM_000474.4(TWIST1):c.211C>T (p.Gln71Ter)

Gene:

TWIST1:twist family bHLH transcription factor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p21.1

Genomic location:

Preferred name:

NM_000474.4(TWIST1):c.211C>T (p.Gln71Ter)

HGVS:

NC_000007.14:g.19117111G>A
NG_008114.2:g.5562C>T
NM_000474.4:c.211C>TMANE SELECT
NP_000465.1:p.Gln71Ter
NC_000007.13:g.19156734G>A
NM_000474.3:c.211C>T
NR_149001.2:n.526C>T

Protein change:

Q71*; GLN71TER

Links:

OMIM: 601622.0012; dbSNP: rs104894065

NCBI 1000 Genomes Browser:

rs104894065

Molecular consequence:

NR_149001.2:n.526C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000474.4:c.211C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: TWIST1-related craniosynostosis (CRS1)
Synonyms:: Craniosynostosis 1
Identifiers:: MONDO: MONDO:0007399; MedGen: C4551902; Orphanet: 63440; OMIM: 123100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002572713	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12791045, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002572713

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 1, 2022)

germline

clinical testing

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	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

A novel mutation in the TWIST gene, implicated in Saethre-Chotzen syndrome, is found in the original case of Robinow-Sorauf syndrome.

Cai J, Shoo BA, Sorauf T, Jabs EW.

Clin Genet. 2003 Jul;64(1):79-82. No abstract available.

PubMed [citation]

PMID:: 12791045

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From 3billion, SCV002572713.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Stop-gained (nonsense) variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with TWIST1-related disorder (ClinVar ID: VCV000007984 / PMID: 12791045). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Mar 5, 2024

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