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NM_000127.3(EXT1):c.1063T>C (p.Cys355Arg) AND Multiple congenital exostosis

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 27, 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:
RCV000813609.7

Allele description [Variation Report for NM_000127.3(EXT1):c.1063T>C (p.Cys355Arg)]

NM_000127.3(EXT1):c.1063T>C (p.Cys355Arg)

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.1063T>C (p.Cys355Arg)
HGVS:
  • NC_000008.11:g.117835545A>G
  • NG_007455.2:g.281275T>C
  • NM_000127.3:c.1063T>CMANE SELECT
  • NP_000118.2:p.Cys355Arg
  • NP_000118.2:p.Cys355Arg
  • LRG_493t1:c.1063T>C
  • LRG_493:g.281275T>C
  • LRG_493p1:p.Cys355Arg
  • NC_000008.10:g.118847784A>G
  • NM_000127.2:c.1063T>C
Protein change:
C355R
Links:
dbSNP: rs1587003655
NCBI 1000 Genomes Browser:
rs1587003655
Molecular consequence:
  • NM_000127.3:c.1063T>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000953976Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 27, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Large-scale mutational analysis in the EXT1 and EXT2 genes for Japanese patients with multiple osteochondromas.

Ishimaru D, Gotoh M, Takayama S, Kosaki R, Matsumoto Y, Narimatsu H, Sato T, Kimata K, Akiyama H, Shimizu K, Matsumoto K.

BMC Genet. 2016 Mar 9;17:52. doi: 10.1186/s12863-016-0359-4.

PubMed [citation]
PMID:
26961984
PMCID:
PMC4784393
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000953976.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This missense change has been observed in individual(s) with multiple osteochondromas (PMID: 17301954; Invitae). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys355 amino acid residue in EXT1. Other variant(s) that disrupt this residue have been observed in individuals with EXT1-related conditions (PMID: 26961984), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt EXT1 protein function. ClinVar contains an entry for this variant (Variation ID: 657060). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 355 of the EXT1 protein (p.Cys355Arg).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024