NM_000127.3(EXT1):c.2101C>T (p.Arg701Ter) AND Multiple congenital exostosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 8, 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:: RCV000630806.10

Allele description [Variation Report for NM_000127.3(EXT1):c.2101C>T (p.Arg701Ter)]

NM_000127.3(EXT1):c.2101C>T (p.Arg701Ter)

Gene:

EXT1:exostosin glycosyltransferase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q24.11

Genomic location:

Preferred name:

NM_000127.3(EXT1):c.2101C>T (p.Arg701Ter)

HGVS:

NC_000008.11:g.117799852G>A
NG_007455.2:g.316968C>T
NM_000127.3:c.2101C>TMANE SELECT
NP_000118.2:p.Arg701Ter
NP_000118.2:p.Arg701Ter
LRG_493t1:c.2101C>T
LRG_493:g.316968C>T
LRG_493p1:p.Arg701Ter
NC_000008.10:g.118812091G>A
NM_000127.2:c.2101C>T

Protein change:

R701*

Links:

dbSNP: rs1363815113

NCBI 1000 Genomes Browser:

rs1363815113

Molecular consequence:

NM_000127.3:c.2101C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Multiple congenital exostosis (EXT)
Synonyms:: MULTIPLE CARTILAGINOUS EXOSTOSES; Hereditary multiple osteochondromas; Multiple exostoses; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0005508; MedGen: C0015306; Orphanet: 321; OMIM: PS133700; Human Phenotype Ontology: HP:0002762

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000751773	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 8, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11170095, 26690531, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000751773

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 8, 2023)

germline

clinical testing

PubMed (3)
[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

Mutation frequencies of EXT1 and EXT2 in 43 Japanese families with hereditary multiple exostoses.

Seki H, Kubota T, Ikegawa S, Haga N, Fujioka F, Ohzeki S, Wakui K, Yoshikawa H, Takaoka K, Fukushima Y.

Am J Med Genet. 2001 Feb 15;99(1):59-62.

PubMed [citation]

PMID:: 11170095

Genetic screening of EXT1 and EXT2 in Cypriot families with hereditary multiple osteochondromas.

Tanteles GA, Nicolaou M, Neocleous V, Shammas C, Loizidou MA, Alexandrou A, Ellina E, Patsia N, Sismani C, Phylactou LA, Christophidou-Anastasiadou V.

J Genet. 2015 Dec;94(4):749-54. No abstract available.

PubMed [citation]

PMID:: 26690531

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000751773.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg701*) in the EXT1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 46 amino acid(s) of the EXT1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary multiple osteochondromas (PMID: 11170095, 26690531). ClinVar contains an entry for this variant (Variation ID: 488691). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 20, 2024

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