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NM_001048174.2(MUTYH):c.170A>G (p.His57Arg) AND not provided

Germline classification:
Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:
Jan 10, 2023
Review status:
criteria provided, conflicting classifications
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000505782.4

Allele description [Variation Report for NM_001048174.2(MUTYH):c.170A>G (p.His57Arg)]

NM_001048174.2(MUTYH):c.170A>G (p.His57Arg)

Gene:
MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001048174.2(MUTYH):c.170A>G (p.His57Arg)
HGVS:
  • NC_000001.11:g.45333507T>C
  • NG_008189.1:g.11964A>G
  • NM_001048171.2:c.170A>G
  • NM_001048172.2:c.173A>G
  • NM_001048173.2:c.170A>G
  • NM_001048174.2:c.170A>GMANE SELECT
  • NM_001128425.2:c.254A>G
  • NM_001293190.2:c.215A>G
  • NM_001293191.2:c.203A>G
  • NM_001293192.2:c.-97-10A>G
  • NM_001293195.2:c.170A>G
  • NM_001293196.2:c.-97-10A>G
  • NM_001350650.2:c.-102A>G
  • NM_001350651.2:c.-92-10A>G
  • NM_012222.3:c.245A>G
  • NP_001041636.2:p.His57Arg
  • NP_001041637.1:p.His58Arg
  • NP_001041638.1:p.His57Arg
  • NP_001041639.1:p.His57Arg
  • NP_001121897.1:p.His85Arg
  • NP_001121897.1:p.His85Arg
  • NP_001280119.1:p.His72Arg
  • NP_001280120.1:p.His68Arg
  • NP_001280124.1:p.His57Arg
  • NP_036354.1:p.His82Arg
  • LRG_220t1:c.254A>G
  • LRG_220:g.11964A>G
  • LRG_220p1:p.His85Arg
  • NC_000001.10:g.45799179T>C
  • NM_001128425.1:c.254A>G
  • NR_146882.2:n.398A>G
  • NR_146883.2:n.321A>G
Protein change:
H57R
Links:
dbSNP: rs558707786
NCBI 1000 Genomes Browser:
rs558707786
Molecular consequence:
  • NM_001350650.2:c.-102A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001293192.2:c.-97-10A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293196.2:c.-97-10A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001350651.2:c.-92-10A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001048171.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.2:c.173A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.2:c.254A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.2:c.215A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.2:c.203A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.3:c.245A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.2:n.398A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.321A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000322182GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely pathogenic
(Nov 30, 2016) 		germlineclinical testing

Citation Link,

SCV004222082Quest Diagnostics Nichols Institute San Juan Capistrano
criteria provided, single submitter

(Quest Diagnostics criteria)		Uncertain significance
(Jan 10, 2023) 		unknownclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

MUTYH-associated polyposis - variability of the clinical phenotype in patients with biallelic and monoallelic MUTYH mutations and report on novel mutations.

Morak M, Laner A, Bacher U, Keiling C, Holinski-Feder E.

Clin Genet. 2010 Oct;78(4):353-63. doi: 10.1111/j.1399-0004.2010.01478.x.

PubMed [citation]
PMID:
20618354

Multi-gene panel testing confirms phenotypic variability in MUTYH-Associated Polyposis.

Sutcliffe EG, Bartenbaker Thompson A, Stettner AR, Marshall ML, Roberts ME, Susswein LR, Wang Y, Klein RT, Hruska KS, Solomon BD.

Fam Cancer. 2019 Apr;18(2):203-209. doi: 10.1007/s10689-018-00116-2.

PubMed [citation]
PMID:
30604180
See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000322182.5

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

Description

This variant is denoted MUTYH c.254A>G at the cDNA level, p.His85Arg (H85R) at the protein level, and results in the change of a Histidine to an Arginine (CAT>CGT). This variant was observed in the homozygous state in a patient who had a history of 10-100 colorectal adenomas and a sibling with colorectal cancer (Morak 2010). MUTYH His85Arg was not observed at a significant frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Histidine and Arginine share similar properties, this is considered a conservative amino acid substitution. MUTYH His85Arg occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on the currently available evidence and internal data, we consider MUTYH His85Arg to be a likely pathogenic variant. Of note, MUTYH-Associated Polyposis (MAP) is a recessive condition associated with two pathogenic variants on opposite chromosomes in MUTYH.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004222082.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The frequency of this variant in the general population, 0.000008 (2/251476 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with MUTYH-Associated Polyposis (PMID: 30604180 (2019)). Additionally, the variant was reported in a family with a history of polyps and colorectal cancer (PMID: 20618354 (2010)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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

Last Updated: Apr 13, 2025