NM_000474.4(TWIST1):c.508T>A (p.Ser170Thr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 11, 2023
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:: RCV003797697.3

Allele description [Variation Report for NM_000474.4(TWIST1):c.508T>A (p.Ser170Thr)]

NM_000474.4(TWIST1):c.508T>A (p.Ser170Thr)

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.508T>A (p.Ser170Thr)

HGVS:

NC_000007.14:g.19116814A>T
NG_008114.2:g.5859T>A
NG_177462.1:g.272A>T
NM_000474.4:c.508T>AMANE SELECT
NP_000465.1:p.Ser170Thr
NC_000007.13:g.19156437A>T
NR_149001.2:n.823T>A

Protein change:

S170T

Molecular consequence:

NM_000474.4:c.508T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_149001.2:n.823T>A - 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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PREDICTED: Lates calcarifer NACHT, LRR and PYD domains-containing protein 12 (LO...
PREDICTED: Lates calcarifer NACHT, LRR and PYD domains-containing protein 12 (LOC108884988), transcript variant X49, mRNA
gi|2315989929|ref|XM_051067002.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004587054	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 11, 2023)	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

SCV004587054

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 11, 2023)

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, SCV004587054.1

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

Description

This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 170 of the TWIST1 protein (p.Ser170Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TWIST1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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.

#	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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