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NM_001048174.2(MUTYH):c.461G>A (p.Arg154His)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
9 (Most recent: Sep 25, 2021)
Last evaluated:
Oct 13, 2020
Accession:
VCV000182689.12
Variation ID:
182689
Description:
single nucleotide variant
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NM_001048174.2(MUTYH):c.461G>A (p.Arg154His)

Allele ID
179937
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1p34.1
Genomic location
1: 45332794 (GRCh38) GRCh38 UCSC
1: 45798466 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_001128425.1:c.545G>A NP_001121897.1:p.Arg182His missense
NM_001293192.1:c.185G>A NP_001280121.1:p.Arg62His missense
NC_000001.10:g.45798466C>T
... more HGVS
Protein change
R182H, R62H, R154H, R165H, R179H, R39H, R155H, R169H
Other names
p.R182H:CGT>CAT
Canonical SPDI
NC_000001.11:45332793:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Exome Aggregation Consortium (ExAC) 0.00002
Links
ClinGen: CA013795
dbSNP: rs143353451
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, multiple submitters, no conflicts Jun 30, 2020 RCV000160752.5
Pathogenic 2 criteria provided, multiple submitters, no conflicts May 12, 2020 RCV000214896.5
Pathogenic 4 criteria provided, multiple submitters, no conflicts Oct 13, 2020 RCV000200700.9
Pathogenic 1 criteria provided, single submitter Nov 2, 2016 RCV000508179.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MUTYH - - GRCh38
GRCh37
1646 1751

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Mar 17, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000273003.5
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (6)
Comment:
​The p.R182H pathogenic mutation (also known as c.545G>A), located in coding exon 7 of the MUTYH gene, results from a G to A substitution at … (more)
Pathogenic
(Oct 13, 2020)
criteria provided, single submitter
Method: clinical testing
MYH-associated polyposis
Allele origin: germline
Invitae
Accession: SCV000253867.8
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (8)
Comment:
This sequence change replaces arginine with histidine at codon 182 of the MUTYH protein (p.Arg182His). The arginine residue is highly conserved and there is a … (more)
Pathogenic
(Dec 17, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000211402.12
Submitted: (Sep 25, 2021)
Evidence details
Comment:
Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious … (more)
Pathogenic
(Nov 02, 2016)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV000604307.1
Submitted: (Jun 30, 2017)
Evidence details
Pathogenic
(Jul 02, 2018)
criteria provided, single submitter
Method: clinical testing
MYH-associated polyposis
Allele origin: unknown
Mendelics
Accession: SCV000837774.1
Submitted: (Aug 20, 2018)
Evidence details
Pathogenic
(Jan 29, 2019)
criteria provided, single submitter
Method: clinical testing
MUTYH-associated polyposis
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697702.2
Submitted: (Sep 24, 2019)
Evidence details
Publications
PubMed (5)
Comment:
Variant summary: The variant, MUTYH c.545G>A (p.Arg182His) results in a non-conservative amino acid change located in the HhH-GPD domain of the encoded protein sequence. Five … (more)
Pathogenic
(May 12, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000685639.2
Submitted: (May 19, 2020)
Comment:
This missense variant replaces arginine with histidine at codon 182 of the MUTYH protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
Evidence details
Pathogenic
(Jun 30, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: unknown
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001470576.1
Submitted: (Dec 31, 2020)
Evidence details
Publications
PubMed (10)
Comment:
The best available variant frequency is uninformative because it is below the disease allele frequency. Found in at least one patient with expected phenotype for … (more)
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
MYH-associated polyposis
Allele origin: germline
Genomics England Pilot Project,Genomics England
Accession: SCV001760035.1
Submitted: (Jul 15, 2021)
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
Inherited DNA-Repair Defects in Colorectal Cancer. AlDubayan SH American journal of human genetics 2018 PMID: 29478780
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer. Yurgelun MB Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2017 PMID: 28135145
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Susswein LR Genetics in medicine : official journal of the American College of Medical Genetics 2016 PMID: 26681312
Functional Complementation Assay for 47 MUTYH Variants in a MutY-Disrupted Escherichia coli Strain. Komine K Human mutation 2015 PMID: 25820570
MUTYH-associated colorectal cancer and adenomatous polyposis. Yamaguchi S Surgery today 2014 PMID: 23605219
Impaired suppressive activities of human MUTYH variant proteins against oxidative mutagenesis. Shinmura K World journal of gastroenterology 2012 PMID: 23322991
Adenine DNA glycosylase activity of 14 human MutY homolog (MUTYH) variant proteins found in patients with colorectal polyposis and cancer. Goto M Human mutation 2010 PMID: 20848659
MUTYH-associated polyposis - variability of the clinical phenotype in patients with biallelic and monoallelic MUTYH mutations and report on novel mutations. Morak M Clinical genetics 2010 PMID: 20618354
Increased colorectal cancer incidence in obligate carriers of heterozygous mutations in MUTYH. Jones N Gastroenterology 2009 PMID: 19394335
Analysis of MUTYH genotypes and colorectal phenotypes in patients With MUTYH-associated polyposis. Nielsen M Gastroenterology 2009 PMID: 19032956
Immunohistochemical expression of MYH protein can be used to identify patients with MYH-associated polyposis. Di Gregorio C Gastroenterology 2006 PMID: 16890597
MUTYH-associated polyposis: 70 of 71 patients with biallelic mutations present with an attenuated or atypical phenotype. Aretz S International journal of cancer 2006 PMID: 16557584
Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations. Ponti G Clinical genetics 2005 PMID: 16207212
Germline MUTYH (MYH) mutations in Portuguese individuals with multiple colorectal adenomas. Isidro G Human mutation 2004 PMID: 15366000

Text-mined citations for rs143353451...

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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 26, 2021