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NM_000474.4(TWIST1):c.472T>C (p.Phe158Leu) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 29, 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:
RCV001991195.6

Allele description [Variation Report for NM_000474.4(TWIST1):c.472T>C (p.Phe158Leu)]

NM_000474.4(TWIST1):c.472T>C (p.Phe158Leu)

Genes:
LOC129998021:ATAC-STARR-seq lymphoblastoid active region 25682 [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.472T>C (p.Phe158Leu)
HGVS:
  • NC_000007.14:g.19116850A>G
  • NG_008114.2:g.5823T>C
  • NM_000474.4:c.472T>CMANE SELECT
  • NP_000465.1:p.Phe158Leu
  • NC_000007.13:g.19156473A>G
  • NR_149001.2:n.787T>C
Protein change:
F158L
Links:
dbSNP: rs2115396574
NCBI 1000 Genomes Browser:
rs2115396574
Molecular consequence:
  • NM_000474.4:c.472T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_149001.2:n.787T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002263748Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Apr 29, 2021) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A survey of TWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals.

Elanko N, Sibbring JS, Metcalfe KA, Clayton-Smith J, Donnai D, Temple IK, Wall SA, Wilkie AO.

Hum Mutat. 2001 Dec;18(6):535-41.

PubMed [citation]
PMID:
11748846

Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome.

Kress W, Schropp C, Lieb G, Petersen B, Büsse-Ratzka M, Kunz J, Reinhart E, Schäfer WD, Sold J, Hoppe F, Pahnke J, Trusen A, Sörensen N, Krauss J, Collmann H.

Eur J Hum Genet. 2006 Jan;14(1):39-48.

PubMed [citation]
PMID:
16251895
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002263748.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with clinical features of Saethre-Chotzen syndrome (PMID: 11748846, 16251895, 19483581). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 158 of the TWIST1 protein (p.Phe158Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024