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NM_002435.3(MPI):c.991del (p.Glu331fs) AND MPI-congenital disorder of glycosylation

Germline classification:
Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:
Nov 18, 2023
Review status:
criteria provided, conflicting classifications
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:
RCV000673079.6

Allele description [Variation Report for NM_002435.3(MPI):c.991del (p.Glu331fs)]

NM_002435.3(MPI):c.991del (p.Glu331fs)

Gene:
MPI:mannose phosphate isomerase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
15q24.1
Genomic location:
Preferred name:
NM_002435.3(MPI):c.991del (p.Glu331fs)
HGVS:
  • NC_000015.10:g.74897157del
  • NG_008921.1:g.12089del
  • NM_001289155.2:c.845-355del
  • NM_001289156.2:c.841del
  • NM_001289157.2:c.808del
  • NM_001330372.2:c.931del
  • NM_002435.3:c.991delMANE SELECT
  • NP_001276085.1:p.Glu281fs
  • NP_001276086.1:p.Glu270fs
  • NP_001317301.1:p.Glu311fs
  • NP_002426.1:p.Glu331fs
  • NC_000015.9:g.75189497del
  • NC_000015.9:g.75189498del
  • NM_002435.1:c.991delG
Protein change:
E270fs
Links:
dbSNP: rs1555479423
NCBI 1000 Genomes Browser:
rs1555479423
Molecular consequence:
  • NM_001289156.2:c.841del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001289157.2:c.808del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001330372.2:c.931del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_002435.3:c.991del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001289155.2:c.845-355del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
MPI-congenital disorder of glycosylation
Synonyms:
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ib; CDG Ib; Congenital disorder of glycosylation type 1B; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011257; MedGen: C1865145; Orphanet: 79319; OMIM: 602579

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000798247Counsyl
criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))
Uncertain significance
(Mar 6, 2018)
unknownclinical testing

Citation Link,

SCV002186902Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Nov 13, 2023)
germlineclinical testing

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

SCV005053357Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Nov 18, 2023)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Hyperinsulinemic hypoglycemia as a presenting sign in phosphomannose isomerase deficiency: A new manifestation of carbohydrate-deficient glycoprotein syndrome treatable with mannose.

de Lonlay P, Cuer M, Vuillaumier-Barrot S, Beaune G, Castelnau P, Kretz M, Durand G, Saudubray JM, Seta N.

J Pediatr. 1999 Sep;135(3):379-83.

PubMed [citation]
PMID:
10484808

MPI-CDG with transient hypoglycosylation and antithrombin deficiency.

de la Morena-Barrio ME, Wypasek E, Owczarek D, MiƱano A, Vicente V, Corral J, Undas A.

Haematologica. 2019 Feb;104(2):e79-e82. doi: 10.3324/haematol.2018.211326. Epub 2018 Dec 13. No abstract available.

PubMed [citation]
PMID:
30545931
PMCID:
PMC6355499
See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000798247.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV002186902.3

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

Description

This sequence change creates a premature translational stop signal (p.Glu331Lysfs*18) in the MPI gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 93 amino acid(s) of the MPI 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 MPI-related conditions. ClinVar contains an entry for this variant (Variation ID: 556997). This variant disrupts a region of the MPI protein in which other variant(s) (p.Ile398Thr) have been determined to be pathogenic (PMID: 10484808, 30545931). 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.

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

From Baylor Genetics, SCV005053357.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 17, 2024