NM_000127.3(EXT1):c.1A>C (p.Met1Leu) AND Multiple congenital exostosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 24, 2022
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:: RCV003050322.2

Allele description [Variation Report for NM_000127.3(EXT1):c.1A>C (p.Met1Leu)]

NM_000127.3(EXT1):c.1A>C (p.Met1Leu)

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.1A>C (p.Met1Leu)

HGVS:

NC_000008.11:g.118111046T>G
NG_007455.2:g.5774A>C
NM_000127.3:c.1A>CMANE SELECT
NP_000118.2:p.Met1Leu
NP_000118.2:p.Met1Leu
LRG_493t1:c.1A>C
LRG_493:g.5774A>C
LRG_493p1:p.Met1Leu
NC_000008.10:g.119123285T>G
NM_000127.2:c.1A>C

Protein change:

M1L

Molecular consequence:

NM_000127.3:c.1A>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000127.3:c.1A>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003350074	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 24, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17301954, 19810120, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003350074

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 24, 2022)

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

A combined analytical approach reveals novel EXT1/2 gene mutations in a large cohort of Italian multiple osteochondromas patients.

Signori E, Massi E, Matera MG, Poscente M, Gravina C, Falcone G, Rosa MA, Rinaldi M, Wuyts W, Seripa D, Dallapiccola B, Fazio VM.

Genes Chromosomes Cancer. 2007 May;46(5):470-7.

PubMed [citation]

PMID:: 17301954

Multiple osteochondromas: mutation update and description of the multiple osteochondromas mutation database (MOdb).

Jennes I, Pedrini E, Zuntini M, Mordenti M, Balkassmi S, Asteggiano CG, Casey B, Bakker B, Sangiorgi L, Wuyts W.

Hum Mutat. 2009 Dec;30(12):1620-7. doi: 10.1002/humu.21123. Review.

PubMed [citation]

PMID:: 19810120

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003350074.3

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

Description

For these reasons, this variant has been classified as Pathogenic. Disruption of the initiator codon has been observed in individual(s) with hereditary multiple osteochondromatosis (PMID: 17301954, 19810120; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the EXT1 mRNA. The next in-frame methionine is located at codon 100.

#	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 30, 2024

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