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NM_000303.3(PMM2):c.310C>G (p.Leu104Val) AND PMM2-congenital disorder of glycosylation

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 20, 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:
RCV002524829.3

Allele description [Variation Report for NM_000303.3(PMM2):c.310C>G (p.Leu104Val)]

NM_000303.3(PMM2):c.310C>G (p.Leu104Val)

Gene:
PMM2:phosphomannomutase 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.2
Genomic location:
Preferred name:
NM_000303.3(PMM2):c.310C>G (p.Leu104Val)
HGVS:
  • NC_000016.10:g.8806370C>G
  • NG_009209.1:g.13558C>G
  • NM_000303.3:c.310C>GMANE SELECT
  • NP_000294.1:p.Leu104Val
  • NC_000016.9:g.8900227C>G
  • NM_000303.2:c.310C>G
Protein change:
L104V
Links:
dbSNP: rs770458492
NCBI 1000 Genomes Browser:
rs770458492
Molecular consequence:
  • NM_000303.3:c.310C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
PMM2-congenital disorder of glycosylation
Synonyms:
CDG Ia; CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME, TYPE Ia; CDG 1A; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008907; MedGen: C0349653; Orphanet: 79318; OMIM: 212065

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003443434Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 20, 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

Functional analysis of novel mutations in a congenital disorder of glycosylation Ia patient with mixed Asian ancestry.

Westphal V, Enns GM, McCracken MF, Freeze HH.

Mol Genet Metab. 2001 May;73(1):71-6.

PubMed [citation]
PMID:
11350185

Primary ovarian insufficiency in a female with phosphomannomutase-2 gene (PMM2) mutations for congenital disorder of glycosylation.

Masunaga Y, Mochizuki M, Kadoya M, Wada Y, Okamoto N, Fukami M, Kato F, Saitsu H, Ogata T.

Endocr J. 2021 May 28;68(5):605-611. doi: 10.1507/endocrj.EJ20-0706. Epub 2021 Mar 11.

PubMed [citation]
PMID:
33583911
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003443434.2

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 104 of the PMM2 protein (p.Leu104Val). For these reasons, this variant has been classified as Pathogenic. Studies have shown that this missense change alters PMM2 gene expression (PMID: 11350185). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PMM2 protein function. ClinVar contains an entry for this variant (Variation ID: 379257). This missense change has been observed in individual(s) with congenital disorder of glycosylation Ia (PMID: 11350185, 33583911). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs770458492, gnomAD 0.01%).

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

Last Updated: Sep 29, 2024