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NM_002435.3(MPI):c.1022del (p.Pro341fs) AND MPI-congenital disorder of glycosylation

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Feb 4, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV003144009.4

Allele description [Variation Report for NM_002435.3(MPI):c.1022del (p.Pro341fs)]

NM_002435.3(MPI):c.1022del (p.Pro341fs)

Gene:
MPI:mannose phosphate isomerase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
15q24.1
Genomic location:
Preferred name:
NM_002435.3(MPI):c.1022del (p.Pro341fs)
HGVS:
  • NC_000015.10:g.74897188del
  • NG_008921.1:g.12120del
  • NG_008921.2:g.12148del
  • NM_001289155.2:c.845-324del
  • NM_001289156.2:c.872del
  • NM_001289157.2:c.839del
  • NM_001330372.2:c.962del
  • NM_002435.3:c.1022delMANE SELECT
  • NP_001276085.1:p.Pro291fs
  • NP_001276086.1:p.Pro280fs
  • NP_001317301.1:p.Pro321fs
  • NP_002426.1:p.Pro341fs
  • NC_000015.9:g.75189524del
  • NC_000015.9:g.75189529del
Protein change:
P280fs
Molecular consequence:
  • NM_001289156.2:c.872del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001289157.2:c.839del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001330372.2:c.962del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_002435.3:c.1022del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001289155.2:c.845-324del - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003832729Revvity Omics, Revvity
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Apr 12, 2022) 		germlineclinical testing

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

SCV004474022Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Feb 4, 2023) 		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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

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
See all PubMed Citations (4)

Details of each submission

From Revvity Omics, Revvity, SCV003832729.2

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

From Invitae, SCV004474022.1

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

Description

This sequence change creates a premature translational stop signal (p.Pro341Leufs*8) in the MPI gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acid(s) of the MPI protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MPI-related conditions. 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

Last Updated: Mar 16, 2024