NM_000474.4(TWIST1):c.400ATC[1] (p.Ile135del) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 8, 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:: RCV002047158.6

Allele description [Variation Report for NM_000474.4(TWIST1):c.400ATC[1] (p.Ile135del)]

NM_000474.4(TWIST1):c.400ATC[1] (p.Ile135del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

7p21.1

Genomic location:

Preferred name:

NM_000474.4(TWIST1):c.400ATC[1] (p.Ile135del)

HGVS:

NC_000007.14:g.19116917GAT[1]
NG_008114.2:g.5751ATC[1]
NM_000474.4:c.400ATC[1]MANE SELECT
NP_000465.1:p.Ile135del
NC_000007.13:g.19156540GAT[1]
NC_000007.13:g.19156540_19156542del
NR_149001.2:n.715ATC[1]

Protein change:

I135del

Links:

dbSNP: rs2115396671

NCBI 1000 Genomes Browser:

rs2115396671

Molecular consequence:

NM_000474.4:c.400ATC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NR_149001.2:n.715ATC[1] - 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

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SAMN14485788 (1)
SRA
abdominal-A, partial [Cataglyphis aenescens]
abdominal-A, partial [Cataglyphis aenescens]
gi|1632313845|gb|QCI61963.1|

Protein
abdominal-A, partial [Cataglyphis kurdistanica]
abdominal-A, partial [Cataglyphis kurdistanica]
gi|1632313827|gb|QCI61954.1|

Protein
abdominal-A, partial [Cataglyphis hispanica]
abdominal-A, partial [Cataglyphis hispanica]
gi|1632313817|gb|QCI61949.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002113188	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 8, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002113188

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 8, 2021)

germline

clinical testing

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

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

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, SCV002113188.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This missense change is located in a region of the TWIST1 protein in which a significant number of missense variants have been reported (Invitae). These observations suggest that this may be a clinically significant region of the protein. This variant has been observed in individual(s) with TWIST1-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This variant, c.403_405del, results in the deletion of 1 amino acid(s) of the TWIST1 protein (p.Ile135del), but otherwise preserves the integrity of the reading frame.

#	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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