NM_002448.3(MSX1):c.661C>T (p.Gln221Ter) AND Hypoplastic enamel-onycholysis-hypohidrosis syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 29, 2016
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:: RCV000544581.6

Allele description [Variation Report for NM_002448.3(MSX1):c.661C>T (p.Gln221Ter)]

NM_002448.3(MSX1):c.661C>T (p.Gln221Ter)

Gene:

MSX1:msh homeobox 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.2

Genomic location:

Preferred name:

NM_002448.3(MSX1):c.661C>T (p.Gln221Ter)

HGVS:

NC_000004.12:g.4862892C>T
NG_008121.1:g.8228C>T
NM_002448.3:c.661C>TMANE SELECT
NP_002439.2:p.Gln221Ter
LRG_1342t1:c.661C>T
LRG_1342:g.8228C>T
LRG_1342p1:p.Gln221Ter
NC_000004.11:g.4864619C>T

Protein change:

Q221*

Links:

dbSNP: rs1553878162

NCBI 1000 Genomes Browser:

rs1553878162

Molecular consequence:

NM_002448.3:c.661C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hypoplastic enamel-onycholysis-hypohidrosis syndrome (TNS)
Synonyms:: NAIL DYSPLASIA WITH HYPODONTIA; Witkop syndrome; Dysplasia of nails with hypodontia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008582; MedGen: C0406735; Orphanet: 2228; OMIM: 189500

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000634356	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 29, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23991204, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000634356

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 29, 2016)

germline

clinical testing

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

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

Candidate gene analysis of tooth agenesis identifies novel mutations in six genes and suggests significant role for WNT and EDA signaling and allele combinations.

Arte S, Parmanen S, Pirinen S, Alaluusua S, Nieminen P.

PLoS One. 2013;8(8):e73705. doi: 10.1371/journal.pone.0073705.

PubMed [citation]

PMID:: 23991204
PMCID:: PMC3750013

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, SCV000634356.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, this variant is a novel truncating variant that is expected to disrupt an essential region of the MSX1 protein. Therefore, it has been classified as Pathogenic. This variant has not been reported in the literature in individuals with a MSX1-related disease. However, a different truncation downstream of this variant (p.Asn222Lysfs*118) has been determined to be pathogenic (PMID: 23991204). This suggests that deletion of this region of the MSX1 protein is causative of disease. This sequence change results in a premature translational stop signal in the last exon of the MSX1 mRNA at codon 221 (p.Gln221*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acids of the MSX1 protein.

#	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: Mar 5, 2024

ClinVar

Relating variation to medicine