NM_000127.3(EXT1):c.1469del (p.Leu490fs) AND Multiple congenital exostosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 22, 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:: RCV000702125.10

Allele description [Variation Report for NM_000127.3(EXT1):c.1469del (p.Leu490fs)]

NM_000127.3(EXT1):c.1469del (p.Leu490fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

8q24.11

Genomic location:

Preferred name:

NM_000127.3(EXT1):c.1469del (p.Leu490fs)

HGVS:

NC_000008.11:g.117819743del
NG_007455.2:g.297077del
NM_000127.3:c.1469delMANE SELECT
NP_000118.2:p.Leu490fs
NP_000118.2:p.Leu490fs
LRG_493t1:c.1469del
LRG_493:g.297077del
LRG_493p1:p.Leu490fs
NC_000008.10:g.118831982del
NM_000127.2:c.1469del
NM_000127.2:c.1469delT

Protein change:

L490fs

Links:

OMIM: 608177.0001; dbSNP: rs886039356

NCBI 1000 Genomes Browser:

rs886039356

Molecular consequence:

NM_000127.3:c.1469del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000830961	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 22, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 7550340, 23439489, 29126381, 10679937, 11391482, 19810120, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000830961

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 22, 2023)

germline

clinical testing

PubMed (7)
[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

Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1).

Ahn J, Lüdecke HJ, Lindow S, Horton WA, Lee B, Wagner MJ, Horsthemke B, Wells DE.

Nat Genet. 1995 Oct;11(2):137-43.

PubMed [citation]

PMID:: 7550340

Mutations in the EXT1 and EXT2 genes in Spanish patients with multiple osteochondromas.

Sarrión P, Sangorrin A, Urreizti R, Delgado A, Artuch R, Martorell L, Armstrong J, Anton J, Torner F, Vilaseca MA, Nevado J, Lapunzina P, Asteggiano CG, Balcells S, Grinberg D.

Sci Rep. 2013;3:1346. doi: 10.1038/srep01346.

PubMed [citation]

PMID:: 23439489
PMCID:: PMC3581825

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000830961.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 265131). This premature translational stop signal has been observed in individuals with multiple osteochondromas and hereditary multiple osteochondromas (PMID: 7550340, 23439489, 29126381). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu490Argfs*9) in the EXT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EXT1 are known to be pathogenic (PMID: 10679937, 11391482, 19810120).

#	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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