U.S. flag

An official website of the United States government

NM_000474.4(TWIST1):c.358C>T (p.Arg120Cys) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 14, 2019
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:
RCV000808616.9

Allele description [Variation Report for NM_000474.4(TWIST1):c.358C>T (p.Arg120Cys)]

NM_000474.4(TWIST1):c.358C>T (p.Arg120Cys)

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.358C>T (p.Arg120Cys)
HGVS:
  • NC_000007.14:g.19116964G>A
  • NG_008114.2:g.5709C>T
  • NM_000474.4:c.358C>TMANE SELECT
  • NP_000465.1:p.Arg120Cys
  • NC_000007.13:g.19156587G>A
  • NM_000474.3:c.358C>T
  • NR_149001.2:n.673C>T
Protein change:
R120C
Links:
dbSNP: rs1233220987
NCBI 1000 Genomes Browser:
rs1233220987
Molecular consequence:
  • NM_000474.4:c.358C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_149001.2:n.673C>T - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000948730Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Mar 14, 2019) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

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 Invitae, SCV000948730.6

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.R120 amino acid residue in TWIST1. Other variant(s) that disrupt this residue have been observed in individuals with TWIST1-related conditions (PMID: 10649491), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individuals affected with Saethre-Chotzen syndrome (PMID: 15923834, 18391498) and was also observed to be de novo in an individual affected with craniosynostosis (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 120 of the TWIST1 protein (p.Arg120Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine.

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

Last Updated: Jun 23, 2024