NM_000127.3(EXT1):c.988_989insTC (p.Asn330fs) AND Multiple congenital exostosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 11, 2018
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:: RCV000693405.7

Allele description [Variation Report for NM_000127.3(EXT1):c.988_989insTC (p.Asn330fs)]

NM_000127.3(EXT1):c.988_989insTC (p.Asn330fs)

Gene:

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

Variant type:

Insertion

Cytogenetic location:

8q24.11

Genomic location:

Preferred name:

NM_000127.3(EXT1):c.988_989insTC (p.Asn330fs)

HGVS:

NC_000008.11:g.117837175_117837176insGA
NG_007455.2:g.279644_279645insTC
NM_000127.3:c.988_989insTCMANE SELECT
NP_000118.2:p.Asn330fs
NP_000118.2:p.Asn330fs
LRG_493t1:c.988_989insTC
LRG_493:g.279644_279645insTC
LRG_493p1:p.Asn330fs
NC_000008.10:g.118849414_118849415insGA
NM_000127.2:c.988_989insTC

Protein change:

N330fs

Links:

dbSNP: rs1563575697

NCBI 1000 Genomes Browser:

rs1563575697

Molecular consequence:

NM_000127.3:c.988_989insTC - 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
SCV000821273	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 11, 2018)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10679937, 11391482, 19810120, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000821273

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 11, 2018)

germline

clinical testing

PubMed (4)
[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

Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes.

Wuyts W, Van Hul W.

Hum Mutat. 2000;15(3):220-7. Review.

PubMed [citation]

PMID:: 10679937

Etiological point mutations in the hereditary multiple exostoses gene EXT1: a functional analysis of heparan sulfate polymerase activity.

Cheung PK, McCormick C, Crawford BE, Esko JD, Tufaro F, Duncan G.

Am J Hum Genet. 2001 Jul;69(1):55-66. Epub 2001 Jun 5.

PubMed [citation]

PMID:: 11391482
PMCID:: PMC1226048

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000821273.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in EXT1 are known to be pathogenic (PMID: 10679937, 11391482, 19810120). This variant has not been reported in the literature in individuals with EXT1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asn330Ilefs*30) in the EXT1 gene. It is expected to result in an absent or disrupted protein product.

#	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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