NM_017739.4(POMGNT1):c.1780del (p.Ala594fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 30, 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:: RCV003782830.3

Allele description [Variation Report for NM_017739.4(POMGNT1):c.1780del (p.Ala594fs)]

NM_017739.4(POMGNT1):c.1780del (p.Ala594fs)

Genes:

POMGNT1:protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-) [Gene - OMIM - HGNC]
TSPAN1:tetraspanin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p34.1

Genomic location:

Preferred name:

NM_017739.4(POMGNT1):c.1780del (p.Ala594fs)

HGVS:

NC_000001.11:g.46189859del
NG_009205.3:g.35447del
NM_001243766.2:c.1780del
NM_001290129.2:c.1714del
NM_001290130.2:c.1351del
NM_001410783.1:c.1780del
NM_017739.4:c.1780delMANE SELECT
NP_001230695.2:p.Ala594fs
NP_001277058.2:p.Ala572fs
NP_001277059.2:p.Ala451fs
NP_001397712.1:p.Ala594fs
NP_060209.4:p.Ala594fs
LRG_701t1:c.1780del
LRG_701t2:c.1780del
LRG_701:g.35447del
LRG_701p1:p.Ala594fs
LRG_701p2:p.Ala594fs
NC_000001.10:g.46655531del
NR_024332.1:n.2431delG

Protein change:

A451fs

Molecular consequence:

NM_001243766.2:c.1780del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001290129.2:c.1714del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001290130.2:c.1351del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001410783.1:c.1780del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_017739.4:c.1780del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004604616	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 30, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12788071, 12849864, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004604616

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 30, 2023)

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

Loss-of-function of an N-acetylglucosaminyltransferase, POMGnT1, in muscle-eye-brain disease.

Manya H, Sakai K, Kobayashi K, Taniguchi K, Kawakita M, Toda T, Endo T.

Biochem Biophys Res Commun. 2003 Jun 20;306(1):93-7.

PubMed [citation]

PMID:: 12788071

Enzymatic diagnostic test for Muscle-Eye-Brain type congenital muscular dystrophy using commercially available reagents.

Zhang W, Vajsar J, Cao P, Breningstall G, Diesen C, Dobyns W, Herrmann R, Lehesjoki AE, Steinbrecher A, Talim B, Toda T, Topaloglu H, Voit T, Schachter H.

Clin Biochem. 2003 Jul;36(5):339-44.

PubMed [citation]

PMID:: 12849864

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004604616.2

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

Description

This sequence change creates a premature translational stop signal (p.Ala594Profs*40) in the POMGNT1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 67 amino acid(s) of the POMGNT1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POMGNT1-related conditions. This variant disrupts a region of the POMGNT1 protein in which other variant(s) (p.Val626Serfs*8) have been determined to be pathogenic (PMID: 12788071, 12849864). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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 5, 2025

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