NM_000255.4(MMUT):c.1276G>A (p.Gly426Arg) AND none provided

Clinical significance:Likely pathogenic (Last evaluated: Jan 9, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001286063.1

Allele description [Variation Report for NM_000255.4(MMUT):c.1276G>A (p.Gly426Arg)]

NM_000255.4(MMUT):c.1276G>A (p.Gly426Arg)

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.1276G>A (p.Gly426Arg)
HGVS:
  • NC_000006.12:g.49451522C>T
  • NG_007100.1:g.16618G>A
  • NM_000255.4:c.1276G>AMANE SELECT
  • NP_000246.2:p.Gly426Arg
  • NC_000006.11:g.49419235C>T
Protein change:
G426R
Links:
Molecular consequence:
  • NM_000255.4:c.1276G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
none provided
Identifiers:
MedGen: CN235283

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001472583ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Likely pathogenic
(Jan 9, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV001472583.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The MMUT c.1276G>A; p.Gly426Arg variant (rs769922244) is reported in the literature in at least one individual affected with methylmalonic aciduria (Worgan 2006). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The glycine at codon 426 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. In vitro functional analyses demonstrate destabilization of the protein and reduced activity (Forny 2014, Worgan 2006). Additionally, another variant at this codon (c.1277G>A; p.Gly426Glu) has been reported in the homozygous state in an individual with methylmalonic aciduria (Forny 2016). Based on available information, this variant is considered to be likely pathogenic. References: Forny P et al. Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency. Hum Mutat. 2014 Dec;35(12):1449-58. Forny P et al. Molecular Genetic Characterization of 151 Mut-Type Methylmalonic Aciduria Patients and Identification of 41 Novel Mutations in MUT. Hum Mutat. 2016 Aug;37(8):745-54. Worgan LC et al. Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype. Hum Mutat. 2006 Jan;27(1):31-43.

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

Last Updated: Jan 30, 2021

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