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NM_000474.4(TWIST1):c.341A>C (p.Asn114Thr) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 27, 2017
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:
RCV000653731.6

Allele description [Variation Report for NM_000474.4(TWIST1):c.341A>C (p.Asn114Thr)]

NM_000474.4(TWIST1):c.341A>C (p.Asn114Thr)

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.341A>C (p.Asn114Thr)
HGVS:
  • NC_000007.14:g.19116981T>G
  • NG_008114.2:g.5692A>C
  • NM_000474.4:c.341A>CMANE SELECT
  • NP_000465.1:p.Asn114Thr
  • NC_000007.13:g.19156604T>G
  • NM_000474.3:c.341A>C
  • NR_149001.2:n.656A>C
Protein change:
N114T
Links:
dbSNP: rs1554442021
NCBI 1000 Genomes Browser:
rs1554442021
Molecular consequence:
  • NM_000474.4:c.341A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_149001.2:n.656A>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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000775621Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Sep 27, 2017)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Integrated strategy for fast and automated molecular characterization of genes involved in craniosynostosis.

Stenirri S, Restagno G, Ferrero GB, Alaimo G, Sbaiz L, Mari C, Genitori L, Maurizio F, Cremonesi L.

Clin Chem. 2007 Oct;53(10):1767-74. Epub 2007 Aug 10.

PubMed [citation]
PMID:
17693524

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000775621.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 reported in the literature in an individual with brachicephaly (PMID: 17693524) This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with threonine at codon 114 of the TWIST1 protein (p.Asn114Thr). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and threonine.

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

Last Updated: Mar 5, 2024