NM_000255.4(MMUT):c.982C>T (p.Leu328Phe) AND Methylmalonic acidemia

Clinical significance:Pathogenic (Last evaluated: Feb 9, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000589433.1

Allele description [Variation Report for NM_000255.4(MMUT):c.982C>T (p.Leu328Phe)]

NM_000255.4(MMUT):c.982C>T (p.Leu328Phe)

Gene:
MMUT:methylmalonyl-CoA mutase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p12.3
Genomic location:
Preferred name:
NM_000255.4(MMUT):c.982C>T (p.Leu328Phe)
HGVS:
  • NC_000006.12:g.49453686G>A
  • NG_007100.1:g.14454C>T
  • NM_000255.4:c.982C>TMANE SELECT
  • NP_000246.2:p.Leu328Phe
  • NC_000006.11:g.49421399G>A
  • NM_000255.3:c.982C>T
  • P22033:p.Leu328Phe
Protein change:
L328F
Links:
UniProtKB: P22033#VAR_022406; dbSNP: rs796052002
NCBI 1000 Genomes Browser:
rs796052002
Molecular consequence:
  • NM_000255.4:c.982C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Methylmalonic acidemia (MMA)
Synonyms:
Isolated Methylmalonic Acidemia
Identifiers:
MONDO: MONDO:0002012; MeSH: C537358; MedGen: C0268583; Human Phenotype Ontology: HP:0002912

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000696309Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Feb 9, 2017)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

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

Citations

PubMed

Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(o) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene.

Acquaviva C, Benoist JF, Pereira S, Callebaut I, Koskas T, Porquet D, Elion J.

Hum Mutat. 2005 Feb;25(2):167-76.

PubMed [citation]
PMID:
15643616

Microarray based mutational analysis of patients with methylmalonic acidemia: identification of 10 novel mutations.

Dündar H, Özgül RK, Güzel-Ozantürk A, Dursun A, Sivri S, Aliefendioğlu D, Coşkun T, Tokatli A.

Mol Genet Metab. 2012 Aug;106(4):419-23. doi: 10.1016/j.ymgme.2012.05.014. Epub 2012 Jun 1.

PubMed [citation]
PMID:
22727635

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696309.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: The MUT c.982C>T (p.Leu328Phe) variant involves the alteration of a conserved nucleotide and is located in substrate-binding TIM barrel of the protein (Lempp_2007, Dndar_2012). 3/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121168 control chromosomes including broad and large population of ExAC. This variant is reported as a pathogenic variant in literature and has been found in several patients with methylmalonic academia in homozygous as well as in compound heterozygous state with other potentially pathogenic variants. Functional studies for this variant are consistent with defective enzymatic activity. One clinical diagnostic laboratory has classified this variant as pathogenic. Taken together, this variant is classified as Pathogenic.

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

Last Updated: Nov 27, 2021

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