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NM_015506.3(MMACHC):c.394C>T (p.Arg132Ter)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
14 (Most recent: Aug 9, 2021)
Last evaluated:
Nov 2, 2020
Accession:
VCV000001423.13
Variation ID:
1423
Description:
single nucleotide variant
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NM_015506.3(MMACHC):c.394C>T (p.Arg132Ter)

Allele ID
16462
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1p34.1
Genomic location
1: 45508329 (GRCh38) GRCh38 UCSC
1: 45974001 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.10:g.45974001C>T
NC_000001.11:g.45508329C>T
NG_013378.1:g.13146C>T
... more HGVS
Protein change
R132*, R75*
Other names
p.R132*:CGA>TGA
Canonical SPDI
NC_000001.11:45508328:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (A)

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00004
Links
ClinGen: CA251787
OMIM: 609831.0003
dbSNP: rs121918241
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 9 criteria provided, multiple submitters, no conflicts Nov 2, 2020 RCV000001488.16
Pathogenic 2 criteria provided, multiple submitters, no conflicts Nov 26, 2018 RCV000153508.9
cblC type of combined methylmalonic aciduria and homocystinuria
Pathogenic 1 criteria provided, single submitter - RCV001250251.1
Pathogenic 1 no assertion criteria provided Jun 7, 2017 RCV000721968.1
Pathogenic 1 no assertion criteria provided Sep 16, 2020 RCV001273221.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MMACHC - - GRCh38
GRCh37
317 341

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Nov 02, 2016)
criteria provided, single submitter
Method: clinical testing
Cobalamin C disease
Allele origin: unknown
Counsyl
Accession: SCV000485871.1
Submitted: (Nov 23, 2016)
Evidence details
Publications
PubMed (1)
Pathogenic
(Nov 02, 2020)
criteria provided, single submitter
Method: clinical testing
Cobalamin C disease
Allele origin: germline
Invitae
Accession: SCV000640288.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change results in a premature translational stop signal in the MMACHC gene (p.Arg132*). While this is not anticipated to result in nonsense mediated … (more)
Pathogenic
(May 18, 2017)
criteria provided, single submitter
Method: clinical testing
Cobalamin C disease
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000611284.1
Submitted: (May 23, 2017)
Evidence details
Pathogenic
(Nov 26, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000238989.13
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted c.394 C>T; p.Arg132Stop (R132X). R132X variant in the MMACHC gene has been reported previously in association with cblC deficiency (Lerner-Ellis, et … (more)
Pathogenic
(-)
criteria provided, single submitter
Method: clinical testing
Cobalamin C disease
Allele origin: germline
Baylor Genetics
Accession: SCV001162905.1
Submitted: (Sep 27, 2019)
Evidence details
Pathogenic
(Aug 03, 2020)
criteria provided, single submitter
Method: clinical testing
Methylmalonic acidemia with homocystinuria
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699398.2
Submitted: (Sep 09, 2020)
Evidence details
Publications
PubMed (1)
Comment:
Variant summary: MMACHC c.394C>T (p.Arg132X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Pathogenic
(Dec 03, 2017)
criteria provided, single submitter
Method: clinical testing
Cobalamin C disease
Allele origin: inherited
Genomic Research Center,Shahid Beheshti University of Medical Sciences
Accession: SCV000746493.1
Submitted: (Dec 03, 2017)
Evidence details
Pathogenic
(Oct 06, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000331092.4
Submitted: (Jun 30, 2017)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(-)
criteria provided, single submitter
Method: clinical testing
cblC type of combined methylmalonic aciduria and homocystinuria
Allele origin: germline
Centogene AG - the Rare Disease Company
Accession: SCV001424456.1
Submitted: (Jul 14, 2020)
Evidence details
Pathogenic
(Nov 02, 2020)
criteria provided, single submitter
Method: clinical testing
Cobalamin C disease
Allele origin: unknown
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001786618.1
Submitted: (Aug 09, 2021)
Evidence details
Publications
PubMed (5)
Comment:
The MMACHC c.394C>T (p.Arg132Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. Across a selection of … (more)
Pathogenic
(Jan 25, 2016)
no assertion criteria provided
Method: research
Cobalamin C disease
Allele origin: germline
Institute of Medical Genetics and Genomics,Sir Ganga Ram Hospital
Study: ORGANIC ACIDURIAS
Accession: SCV000267132.1
Submitted: (Apr 12, 2016)
Comment:
Non-sense mutation
Evidence details
Publications
PubMed (1)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Methylmalonic aciduria with homocystinuria cblC type
Allele origin: germline
Natera, Inc.
Accession: SCV001456013.1
Submitted: (Dec 28, 2020)
Evidence details
Pathogenic
(Jul 01, 2009)
no assertion criteria provided
Method: literature only
METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblC TYPE
Allele origin: germline
OMIM
Accession: SCV000021643.4
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (3)
Lerner-Ellis, J. P., Tirone, J. C.,  (more...)
Pathogenic
(Jun 07, 2017)
no assertion criteria provided
Method: curation
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
Allele origin: germline
SingHealth Duke-NUS Institute of Precision Medicine
Accession: SCV000853111.1
Submitted: (Apr 09, 2018)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Clinical presentation, gene analysis and outcomes in young patients with early-treated combined methylmalonic acidemia and homocysteinemia (cblC type) in Shandong province, China. Han B Brain & development 2016 PMID: 26563984
Prenatal diagnosis using genetic sequencing and identification of a novel mutation in MMACHC. Zong Y BMC medical genetics 2015 PMID: 26149271
A treatable metabolic cause of encephalopathy: cobalamin C deficiency in an 8-year-old male. Krueger JM Pediatrics 2015 PMID: 25511120
Cobalamin C defect: a patient of late-onset type with homozygous p.R132* mutation. Kılıç M The Turkish journal of pediatrics 2013 PMID: 24577983
Mutation spectrum of MMACHC in Chinese patients with combined methylmalonic aciduria and homocystinuria. Liu MY Journal of human genetics 2010 PMID: 20631720
Genetic and cellular studies of oxidative stress in methylmalonic aciduria (MMA) cobalamin deficiency type C (cblC) with homocystinuria (MMACHC). Richard E Human mutation 2009 PMID: 19760748
Spectrum of mutations in MMACHC, allelic expression, and evidence for genotype-phenotype correlations. Lerner-Ellis JP Human mutation 2009 PMID: 19370762
Late-onset cobalamin-C disorder: a challenging diagnosis. Ben-Omran TI American journal of medical genetics. Part A 2007 PMID: 17431913
Combined methylmalonic aciduria and homocystinuria (cblC): phenotype-genotype correlations and ethnic-specific observations. Morel CF Molecular genetics and metabolism 2006 PMID: 16714133
Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type. Lerner-Ellis JP Nature genetics 2006 PMID: 16311595
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MMACHC - - - -
Lerner-Ellis, J. P., Tirone, J. C., Pawelek, P. D., Dore, C., Atkinson, J. L., Watkins, D., Morel, C. F., Fujiwara, T. M., Moras, E., Hosack, A. R., Dunbar, G. V., Antonicka, H., and 10 others Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type. Nature Genet. 38: 93-100, 2006. Note: Erratum: Nature Genet. 38: 957 only, 2006. - - - -

Text-mined citations for rs121918241...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 07, 2021