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NM_002435.3(MPI):c.1253G>A (p.Arg418His) AND MPI-congenital disorder of glycosylation

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Mar 14, 2024
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:
RCV000202324.4

Allele description [Variation Report for NM_002435.3(MPI):c.1253G>A (p.Arg418His)]

NM_002435.3(MPI):c.1253G>A (p.Arg418His)

Gene:
MPI:mannose phosphate isomerase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q24.1
Genomic location:
Preferred name:
NM_002435.3(MPI):c.1253G>A (p.Arg418His)
HGVS:
  • NC_000015.10:g.74897711G>A
  • NG_008921.1:g.12643G>A
  • NM_001289155.2:c.*180G>A
  • NM_001289156.2:c.1103G>A
  • NM_001289157.2:c.1070G>A
  • NM_001330372.2:c.1193G>A
  • NM_002435.3:c.1253G>AMANE SELECT
  • NP_001276085.1:p.Arg368His
  • NP_001276086.1:p.Arg357His
  • NP_001317301.1:p.Arg398His
  • NP_002426.1:p.Arg418His
  • NC_000015.9:g.75190052G>A
  • NM_002435.2:c.1253G>A
  • P34949:p.Arg418His
Protein change:
R357H
Links:
UniProtKB: P34949#VAR_022524; dbSNP: rs863225087
NCBI 1000 Genomes Browser:
rs863225087
Molecular consequence:
  • NM_001289155.2:c.*180G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001289156.2:c.1103G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001289157.2:c.1070G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330372.2:c.1193G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002435.3:c.1253G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000256095Sanford Children's Health Research Center, Sanford-Burnham-Prebys Medical Discovery Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenicinheritedresearch

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

SCV004195524Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Mar 14, 2024)
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 providedinheritedyesnot providednot providednot providednot providednot providedresearch

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

Details of each submission

From Sanford Children's Health Research Center, Sanford-Burnham-Prebys Medical Discovery Institute, SCV000256095.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)

Description

This variant was identified in a male who presented clinically normal until the age of 2 when he became ill with persistent vomiting and venous sinus thrombosis which resulted in a massive stroke. Subsequently he developed a seizure disorder and delayed development. Full metabolic work up was normal except for the presence of a Type I CDG profile. Given his history of normal development prior to the stroke, MPI-CDG was suggested. Enzyme assay concluded he had MPI-CDG. The enzyme assay was performed as previously reported from the Freeze lab, PMID: 9525984. “Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy.” Genetic analysis revealed two single nucleotide variants inherited in a compound heterozygous fashion, NM_002435.2:c.1205A>G and NM_002435.2:c.1253G>A. The c.1253G>A variant has not been previously reported in ExAc, dbSNP or ESP, however it has been reported in COSMIC (Catalogue of Somatic Mutations in Cancer). In COSMIC, the mutation was seen in breast tissue with a sample size of 15 but the mutation was not confirmed to be somatic. The predicted protein change for NM_002435.2 is an Arginine to Histidine, which has been previously reported in SwissProt as a disease associated variant leading to CDG-Ib. This residue is highly conserved (humans through s. cerevisae with the exception of D. melanogaster).

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

From Baylor Genetics, SCV004195524.2

#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 23, 2024