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NM_015506.3(MMACHC):c.616C>T (p.Arg206Trp)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Pathogenic(1);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
3 (Most recent: Jan 7, 2021)
Last evaluated:
Oct 16, 2019
Accession:
VCV000203832.3
Variation ID:
203832
Description:
single nucleotide variant
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NM_015506.3(MMACHC):c.616C>T (p.Arg206Trp)

Allele ID
199956
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1p34.1
Genomic location
1: 45508982 (GRCh38) GRCh38 UCSC
1: 45974654 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.10:g.45974654C>T
NC_000001.11:g.45508982C>T
NM_015506.3:c.616C>T MANE Select NP_056321.2:p.Arg206Trp missense
... more HGVS
Protein change
R206W, R149W
Other names
-
Canonical SPDI
NC_000001.11:45508981:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (G)

Allele frequency
-
Links
ClinGen: CA312738
UniProtKB: Q9Y4U1#VAR_024783
dbSNP: rs538023671
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Oct 16, 2019 RCV000490478.3
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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
Uncertain significance
(Mar 18, 2016)
criteria provided, single submitter
Method: reference population
Cobalamin C disease
Allele origin: germline
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center
Accession: SCV000267397.1
Submitted: (Apr 14, 2016)
Evidence details
Publications
PubMed (2)
Likely pathogenic
(Jan 31, 2018)
criteria provided, single submitter
Method: clinical testing
Cobalamin C disease
Allele origin: unknown
Counsyl
Accession: SCV000800803.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (6)
Pathogenic
(Oct 16, 2019)
criteria provided, single submitter
Method: clinical testing
Cobalamin C disease
Allele origin: germline
Invitae
Accession: SCV001372575.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces arginine with tryptophan at codon 206 of the MMACHC protein (p.Arg206Trp). The arginine residue is highly conserved and there is a … (more)

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
Molecular genetic characterization of cblC defects in 126 pedigrees and prenatal genetic diagnosis of pedigrees with combined methylmalonic aciduria and homocystinuria. Hu S BMC medical genetics 2018 PMID: 30157807
Prenatal diagnosis using genetic sequencing and identification of a novel mutation in MMACHC. Zong Y BMC medical genetics 2015 PMID: 26149271
Clinical presentation and outcome in a series of 88 patients with the cblC defect. Fischer S Journal of inherited metabolic disease 2014 PMID: 24599607
Interaction between methionine synthase isoforms and MMACHC: characterization in cblG-variant, cblG and cblC inherited causes of megaloblastic anaemia. Fofou-Caillierez MB Human molecular genetics 2013 PMID: 23825108
Mutation spectrum of MMACHC in Chinese patients with combined methylmalonic aciduria and homocystinuria. Liu MY Journal of human genetics 2010 PMID: 20631720
Early onset methylmalonic aciduria and homocystinuria cblC type with demyelinating neuropathy. Frattini D Pediatric neurology 2010 PMID: 20610126
Spectrum of mutations in MMACHC, allelic expression, and evidence for genotype-phenotype correlations. Lerner-Ellis JP Human mutation 2009 PMID: 19370762
Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type. Lerner-Ellis JP Nature genetics 2006 PMID: 16311595

Text-mined citations for rs538023671...

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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 May 10, 2021