NM_000474.4(TWIST1):c.301C>T (p.Gln101Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 20, 2021
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:: RCV000698045.5

Allele description [Variation Report for NM_000474.4(TWIST1):c.301C>T (p.Gln101Ter)]

NM_000474.4(TWIST1):c.301C>T (p.Gln101Ter)

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.301C>T (p.Gln101Ter)

HGVS:

NC_000007.14:g.19117021G>A
NG_008114.2:g.5652C>T
NM_000474.4:c.301C>TMANE SELECT
NP_000465.1:p.Gln101Ter
NC_000007.13:g.19156644G>A
NM_000474.3:c.301C>T
NR_149001.2:n.616C>T

Protein change:

Q101*

Links:

dbSNP: rs1563160116

NCBI 1000 Genomes Browser:

rs1563160116

Molecular consequence:

NR_149001.2:n.616C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000474.4:c.301C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Name:: Saethre-Chotzen syndrome (SCS)
Synonyms:: ACS III; Acrocephalo-syndactyly, type 3; Chotzen syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007042; MedGen: C0175699; Orphanet: 794; OMIM: 101400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000826686	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 20, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10749989, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000826686

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 20, 2021)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location.

El Ghouzzi V, Legeai-Mallet L, Aresta S, Benoist C, Munnich A, de Gunzburg J, Bonaventure J.

Hum Mol Genet. 2000 Mar 22;9(5):813-9.

PubMed [citation]

PMID:: 10749989

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000826686.4

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with TWIST1-related conditions. ClinVar contains an entry for this variant (Variation ID: 575739). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln101*) in the TWIST1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TWIST1 are known to be pathogenic (PMID: 10749989).

#	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

Last Updated: Sep 29, 2024

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