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NM_000474.4(TWIST1):c.518del (p.Ala173fs) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 2, 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:
RCV002227696.1

Allele description [Variation Report for NM_000474.4(TWIST1):c.518del (p.Ala173fs)]

NM_000474.4(TWIST1):c.518del (p.Ala173fs)

Genes:
LOC129998021:ATAC-STARR-seq lymphoblastoid active region 25682 [Gene]
TWIST1:twist family bHLH transcription factor 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
7p21.1
Genomic location:
Preferred name:
NM_000474.4(TWIST1):c.518del (p.Ala173fs)
HGVS:
  • NC_000007.14:g.19116804del
  • NG_008114.2:g.5869del
  • NM_000474.4:c.518delMANE SELECT
  • NP_000465.1:p.Ala173fs
  • NC_000007.13:g.19156427del
  • NR_149001.2:n.833del
Protein change:
A173fs
Links:
dbSNP: rs2115396502
NCBI 1000 Genomes Browser:
rs2115396502
Molecular consequence:
  • NM_000474.4:c.518del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_149001.2:n.833del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

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

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002506776New York Genome Center - CSER-NYCKidSeq
criteria provided, single submitter

(NYGC Assertion Criteria 2020)		Uncertain significance
(Jul 2, 2021) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Details of each submission

From New York Genome Center - CSER-NYCKidSeq, SCV002506776.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The heterozygous one nucleotide deletion c.518del (p.Ala173GlufsTer58) identified in the TWIST1 gene alters the wild-type translational reading frame and introduces a premature translation termination codon. The TWIST1 gene has a single protein-coding exon, therefore, it is difficult to predict whether the mutant mRNA is subjected to nonsense-mediated mRNA decay. If translated, the mutant protein is expected to have a total of 230 amino acids (compared to wildtype protein which has 202 amino acids), of which the last 58 amino acid sequence would be unique to the mutant protein. The variant is absent from gnomAD(v3)database suggesting it is not a common benign variant in the populations represented in that database. The c.518del (p.Ala173GlufsTer58) variant has not been reported in affected individuals in the literature. The available evidence is currently insufficient to determine the role of this variant in disease. Therefore, the heterozygous one nucleotide deletion c.518del (p.Ala173GlufsTer58) identified in the TWIST1 gene is reported as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Dec 24, 2023