NM_017739.4(POMGNT1):c.1759_1763del (p.Phe587fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 14, 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:: RCV001939655.3

Allele description [Variation Report for NM_017739.4(POMGNT1):c.1759_1763del (p.Phe587fs)]

NM_017739.4(POMGNT1):c.1759_1763del (p.Phe587fs)

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.1759_1763del (p.Phe587fs)

HGVS:

NC_000001.11:g.46189878_46189882del
NG_009205.3:g.35426_35430del
NM_001243766.2:c.1759_1763del
NM_001290129.2:c.1693_1697del
NM_001290130.2:c.1330_1334del
NM_017739.4:c.1759_1763delMANE SELECT
NP_001230695.2:p.Phe587fs
NP_001277058.2:p.Phe565fs
NP_001277059.2:p.Phe444fs
NP_060209.4:p.Phe587fs
LRG_701t1:c.1759_1763del
LRG_701t2:c.1759_1763del
LRG_701:g.35426_35430del
LRG_701p1:p.Phe587fs
LRG_701p2:p.Phe587fs
NC_000001.10:g.46655548_46655552del
NC_000001.10:g.46655550_46655554del
NG_009205.2:g.35426_35430del

Protein change:

F444fs

Links:

dbSNP: rs1302430730

NCBI 1000 Genomes Browser:

rs1302430730

Molecular consequence:

NM_001243766.2:c.1759_1763del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001290129.2:c.1693_1697del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001290130.2:c.1330_1334del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_017739.4:c.1759_1763del - 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
SCV002236331	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 14, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12849864, 21361872, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002236331

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 14, 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

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

Biochemical correlation of activity of the α-dystroglycan-modifying glycosyltransferase POMGnT1 with mutations in muscle-eye-brain disease.

Voglmeir J, Kaloo S, Laurent N, Meloni MM, Bohlmann L, Wilson IB, Flitsch SL.

Biochem J. 2011 Jun 1;436(2):447-55. doi: 10.1042/BJ20101059.

PubMed [citation]

PMID:: 21361872
PMCID:: PMC3133881

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002236331.3

#	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 results in a frameshift in the POMGNT1 gene (p.Phe587Hisfs*98). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 74 amino acid(s) of the POMGNT1 protein and extend the protein by 23 additional amino acid residues. 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. ClinVar contains an entry for this variant (Variation ID: 1455052). This variant disrupts a region of the POMGNT1 protein in which other variant(s) (p.Arg605His) have been determined to be pathogenic (PMID: 12849864, 21361872; Invitae). 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, 2024

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