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NM_017739.4(POMGNT1):c.1468T>G (p.Cys490Gly) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 23, 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:
RCV002970689.4

Allele description [Variation Report for NM_017739.4(POMGNT1):c.1468T>G (p.Cys490Gly)]

NM_017739.4(POMGNT1):c.1468T>G (p.Cys490Gly)

Genes:
POMGNT1:protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-) [Gene - OMIM - HGNC]
TSPAN1:tetraspanin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_017739.4(POMGNT1):c.1468T>G (p.Cys490Gly)
HGVS:
  • NC_000001.11:g.46192169A>C
  • NG_009205.3:g.33137T>G
  • NM_001243766.2:c.1468T>G
  • NM_001290129.2:c.1402T>G
  • NM_001290130.2:c.1039T>G
  • NM_001410783.1:c.1468T>G
  • NM_017739.4:c.1468T>GMANE SELECT
  • NP_001230695.2:p.Cys490Gly
  • NP_001277058.2:p.Cys468Gly
  • NP_001277059.2:p.Cys347Gly
  • NP_001397712.1:p.Cys490Gly
  • NP_060209.4:p.Cys490Gly
  • LRG_701t1:c.1468T>G
  • LRG_701t2:c.1468T>G
  • LRG_701:g.33137T>G
  • LRG_701p1:p.Cys490Gly
  • LRG_701p2:p.Cys490Gly
  • NC_000001.10:g.46657841A>C
  • NR_024332.1:n.2119T>G
Protein change:
C347G
Molecular consequence:
  • NM_001243766.2:c.1468T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001290129.2:c.1402T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001290130.2:c.1039T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001410783.1:c.1468T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_017739.4:c.1468T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Autosomal recessive limb-girdle muscular dystrophy type 2O
Synonyms:
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 3; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY, LIMB-GIRDLE, POMGNT1-RELATED; Limb-Girdle Muscular Dystrophy Type 3C; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0013161; MedGen: C3150417; Orphanet: 206564; OMIM: 613157
Name:
Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 (MDDGB3)
Synonyms:
MUSCULAR DYSTROPHY, CONGENITAL, POMGNT1-RELATED; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 3
Identifiers:
MONDO: MONDO:0013155; MedGen: C3150412; OMIM: 613151

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003281578Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jan 23, 2022) 		germlineclinical testing

PubMed (8)
[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

POMGnT1 mutation and phenotypic spectrum in muscle-eye-brain disease.

Diesen C, Saarinen A, Pihko H, Rosenlew C, Cormand B, Dobyns WB, Dieguez J, Valanne L, Joensuu T, Lehesjoki AE.

J Med Genet. 2004 Oct;41(10):e115. No abstract available.

PubMed [citation]
PMID:
15466003
PMCID:
PMC1735594

POMGnT1 mutations in congenital muscular dystrophy: genotype-phenotype correlation and expanded clinical spectrum.

Biancheri R, Bertini E, Falace A, Pedemonte M, Rossi A, D'Amico A, Scapolan S, Bergamino L, Petrini S, Cassandrini D, Broda P, Manfredi M, Zara F, Santorelli FM, Minetti C, Bruno C.

Arch Neurol. 2006 Oct;63(10):1491-5.

PubMed [citation]
PMID:
17030669
See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003281578.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Cys490 amino acid residue in POMGNT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15466003, 17030669, 17559086, 17878207, 21361872, 22323514, 24282183). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 POMGNT1 protein function. This variant has not been reported in the literature in individuals affected with POMGNT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 490 of the POMGNT1 protein (p.Cys490Gly).

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

Last Updated: Mar 5, 2025