U.S. flag

An official website of the United States government

NM_001048174.2(MUTYH):c.637C>T (p.Arg213Trp) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Sep 8, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000164664.13

Allele description [Variation Report for NM_001048174.2(MUTYH):c.637C>T (p.Arg213Trp)]

NM_001048174.2(MUTYH):c.637C>T (p.Arg213Trp)

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.637C>T (p.Arg213Trp)
HGVS:
  • NC_000001.11:g.45332458G>A
  • NG_008189.1:g.13013C>T
  • NM_001048171.2:c.637C>T
  • NM_001048172.2:c.640C>T
  • NM_001048173.2:c.637C>T
  • NM_001048174.2:c.637C>TMANE SELECT
  • NM_001128425.2:c.721C>T
  • NM_001293190.2:c.682C>T
  • NM_001293191.2:c.670C>T
  • NM_001293192.2:c.361C>T
  • NM_001293195.2:c.637C>T
  • NM_001293196.2:c.361C>T
  • NM_001350650.2:c.292C>T
  • NM_001350651.2:c.292C>T
  • NM_012222.3:c.712C>T
  • NP_001041636.1:p.Arg227Trp
  • NP_001041636.2:p.Arg213Trp
  • NP_001041637.1:p.Arg214Trp
  • NP_001041638.1:p.Arg213Trp
  • NP_001041639.1:p.Arg213Trp
  • NP_001121897.1:p.Arg241Trp
  • NP_001121897.1:p.Arg241Trp
  • NP_001280119.1:p.Arg228Trp
  • NP_001280120.1:p.Arg224Trp
  • NP_001280121.1:p.Arg121Trp
  • NP_001280124.1:p.Arg213Trp
  • NP_001280125.1:p.Arg121Trp
  • NP_001337579.1:p.Arg98Trp
  • NP_001337580.1:p.Arg98Trp
  • NP_036354.1:p.Arg238Trp
  • NP_036354.1:p.Arg238Trp
  • LRG_220t1:c.721C>T
  • LRG_220:g.13013C>T
  • LRG_220p1:p.Arg241Trp
  • NC_000001.10:g.45798130G>A
  • NM_001048171.1:c.679C>T
  • NM_001128425.1:c.721C>T
  • NM_012222.2:c.712C>T
  • NR_146882.2:n.865C>T
  • NR_146883.2:n.714C>T
  • p.R241W
Protein change:
R121W
Links:
dbSNP: rs34126013
NCBI 1000 Genomes Browser:
rs34126013
Molecular consequence:
  • NM_001048171.2:c.637C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.2:c.640C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.2:c.637C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.2:c.637C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.2:c.721C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.2:c.682C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.2:c.670C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293192.2:c.361C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.2:c.637C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293196.2:c.361C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350650.2:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350651.2:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.3:c.712C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.2:n.865C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.714C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000215329Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Pathogenic
(Dec 14, 2021)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link,

SCV000685663Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Sep 8, 2023)
germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Comprehensive analysis of the contribution of germline MYH variation to early-onset colorectal cancer.

Fleischmann C, Peto J, Cheadle J, Shah B, Sampson J, Houlston RS.

Int J Cancer. 2004 Apr 20;109(4):554-8.

PubMed [citation]
PMID:
14991577

The thorough screening of the MUTYH gene in a large French cohort of sporadic colorectal cancers.

Küry S, Buecher B, Robiou-du-Pont S, Scoul C, Colman H, Lelièvre B, Olschwang S, Le Houérou C, Le Neel T, Faroux R, Ollivry J, Lafraise B, Chupin LD, Bézieau S.

Genet Test. 2007 Winter;11(4):373-9.

PubMed [citation]
PMID:
17931073
See all PubMed Citations (15)

Details of each submission

From Ambry Genetics, SCV000215329.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

The p.R241W pathogenic mutation (also known as c.721C>T), located in coding exon 9 of the MUTYH gene, results from a C to T substitution at nucleotide position 721. The arginine at codon 241 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration has been reported in conjunction with the common MUTYH founder mutations p.G396D (p.G382D) and p.Y179C (p.Y165C), other pathogenic/likely pathogenic MUTYH variants, and as homozygous in multiple patients with classic polyposis, attenuated polyposis, and/or colorectal cancer (Isidro G et al. Hum Mutat. 2004 Oct;24(4):353-4; Bai H et al. Nucleic Acids Res. 2005 Jan 26;33(2):597-604; Torrezan GT et al. Orphanet J Rare Dis. 2013 ;8:54; Guarinos C et al. Clin Cancer Res. 2014 Mar 1;20(5):1158-68; Win AK et al. Int J Cancer. 2016 Oct 1;139(7):1557-63; Khan N et al. Sci Rep. 2017 May 22;7(1):2214; Ambry internal data). Furthermore, the aforementioned co-occurrences are likely to be in trans due to multiple observances with different pathogenic or likely pathogenic MUTYH variants. In functional assays measuring glycosylase activity and DNA-binding activity, this variant demonstrated impaired protein function similar to the p.Y179C (p.Y165C) MUTYH founder mutation (Bai H et al. Nucleic Acids Res. 2005 Jan 26;33(2):597-604; Komine K et al. Hum Mutat. 2015 Jul;36(7):704-11). This alteration has also been identified in individuals diagnosed with male breast cancer, breast cancer and prostate cancer (Rizzolo P et al. Front Oncol, 2018 Dec;8:583; Lang GT et al. Ann Transl Med, 2020 Nov;8:1417; Nguyen-Dumont T et al. Int J Cancer, 2020 10;147:2142-2149). Of note, this alteration is also designated as p.R227W in published literature. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

From Color Diagnostics, LLC DBA Color Health, SCV000685663.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

This missense variant replaces arginine with tryptophan at codon 241 of the MUTYH protein. This variant is also known as c.637C>T (p.Arg213Trp) based on an alternative transcript (NM_001048174.2). Computational prediction tool suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >=0.7, PMID: 27666373). Functional studies have shown that this variant was deficient in A/8-oxoG binding and glycosylase activities , and failed to complement mutY-deficiency in Escherichia coli (PMID: 15673720, 25820570). This variant has been reported as biallelic with another pathogenic variant in multiple individuals affected with polyposis and/or colorectal cancer (PMID: 15366000, 19394335, 23561487, 24470512, 27194394, 28533537, 34704405). This variant has been identified in 18/281720 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.

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

Last Updated: May 12, 2024