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NM_001048174.2(MUTYH):c.452A>G (p.Tyr151Cys) AND Carcinoma of colon

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jul 24, 2014
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000144631.10

Allele description [Variation Report for NM_001048174.2(MUTYH):c.452A>G (p.Tyr151Cys)]

NM_001048174.2(MUTYH):c.452A>G (p.Tyr151Cys)

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.452A>G (p.Tyr151Cys)
Other names:
p.Y165C:TAC>TGC
HGVS:
  • NC_000001.11:g.45332803T>C
  • NG_008189.1:g.12668A>G
  • NM_001048171.2:c.452A>G
  • NM_001048172.2:c.455A>G
  • NM_001048173.2:c.452A>G
  • NM_001048174.2:c.452A>GMANE SELECT
  • NM_001128425.2:c.536A>G
  • NM_001293190.2:c.497A>G
  • NM_001293191.2:c.485A>G
  • NM_001293192.2:c.176A>G
  • NM_001293195.2:c.452A>G
  • NM_001293196.2:c.176A>G
  • NM_001350650.2:c.107A>G
  • NM_001350651.2:c.107A>G
  • NM_012222.3:c.527A>G
  • NP_001041636.1:p.Tyr165Cys
  • NP_001041636.2:p.Tyr151Cys
  • NP_001041637.1:p.Tyr152Cys
  • NP_001041638.1:p.Tyr151Cys
  • NP_001041639.1:p.Tyr151Cys
  • NP_001121897.1:p.Tyr179Cys
  • NP_001121897.1:p.Tyr179Cys
  • NP_001280119.1:p.Tyr166Cys
  • NP_001280120.1:p.Tyr162Cys
  • NP_001280121.1:p.Tyr59Cys
  • NP_001280121.1:p.Tyr59Cys
  • NP_001280124.1:p.Tyr151Cys
  • NP_001280125.1:p.Tyr59Cys
  • NP_001337579.1:p.Tyr36Cys
  • NP_001337580.1:p.Tyr36Cys
  • NP_036354.1:p.Tyr176Cys
  • NP_036354.1:p.Tyr176Cys
  • LRG_220t1:c.536A>G
  • LRG_220:g.12668A>G
  • LRG_220p1:p.Tyr179Cys
  • NC_000001.10:g.45798475T>C
  • NM_001048171.1:c.494A>G
  • NM_001048174.1:c.452A>G
  • NM_001048174.2:c.452A>G
  • NM_001128425.1:c.536A>G
  • NM_001293192.1:c.176A>G
  • NM_012222.2:c.527A>G
  • NR_146882.2:n.680A>G
  • NR_146883.2:n.529A>G
Protein change:
Y151C; TYR165CYS
Links:
OMIM: 604933.0001; dbSNP: rs34612342
NCBI 1000 Genomes Browser:
rs34612342
Molecular consequence:
  • NM_001048171.2:c.452A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.2:c.455A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.2:c.452A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.2:c.452A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.2:c.536A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.2:c.497A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.2:c.485A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293192.2:c.176A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.2:c.452A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293196.2:c.176A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350650.2:c.107A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350651.2:c.107A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.3:c.527A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.2:n.680A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.529A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Carcinoma of colon (CRC)
Synonyms:
Colonic carcinoma; Colon carcinoma
Identifiers:
MONDO: MONDO:0002032; MedGen: C0699790

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000189958Pathway Genomics
no assertion criteria provided
Pathogenic
(Jul 24, 2014) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV000592686Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Pathogenicunknownclinical testing

Help

Summary from all submissions

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

Citations

PubMed

Expanded extracolonic tumor spectrum in MUTYH-associated polyposis.

Vogt S, Jones N, Christian D, Engel C, Nielsen M, Kaufmann A, Steinke V, Vasen HF, Propping P, Sampson JR, Hes FJ, Aretz S.

Gastroenterology. 2009 Dec;137(6):1976-85.e1-10. doi: 10.1053/j.gastro.2009.08.052. Epub 2009 Sep 2.

PubMed [citation]
PMID:
19732775

Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes.

Johnston JJ, Rubinstein WS, Facio FM, Ng D, Singh LN, Teer JK, Mullikin JC, Biesecker LG.

Am J Hum Genet. 2012 Jul 13;91(1):97-108. doi: 10.1016/j.ajhg.2012.05.021. Epub 2012 Jun 14.

PubMed [citation]
PMID:
22703879
PMCID:
PMC3397257
See all PubMed Citations (5)

Details of each submission

From Pathway Genomics, SCV000189958.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000592686.2

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

Description

The MUTYH p.Tyr179Cys variant was identified in 878 of 42,504 proband chromosomes (frequency: 0.03) from individuals or families with MAP or colorectal cancer (CRC). Of these 292 were heterozygous carriers, 99 were homozygous and 487 were compound heterozygotes. The variant was present in 156 of 31,262 control chromosomes (frequency: 0.005) from healthy individuals (Al-Tassan 2002, Nielsen 2009, Nascimbeni 2010, Theodoratou 2010, Vogt 2009, Sieber 2003). The variant was also identified in dbSNP (ID: rs34612342) as With Pathogenic allele, ClinVar (classified as pathogenic by GeneDx, Invitae, Ambry Genetics, Color Genomics, Pathway Genomics and more), Clinvitae (classified as pathogenic by ClinVar and Invitae), Cosmic (pathogenic), and in Insight Colon Cancer Gene Variant Database (535x pathogenic). The variant was not identified in MutDB, or UMD-LSDB databases. The variant was identified in control databases in 412 of 277178 chromosomes at a frequency of 0.001486 (Genome Aggregation Consortium Feb 27, 2017). The p.Tyr179 residue is conserved in mammals but not in more distantly related organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In a meta-analysis study (Theodoratou 2010), to assess and refine CRC risk estimates associated with bi-allelic and mono-allelic MUTYH variants, MUTYH bi-allelic carriers demonstrated a 28-fold increase in CRC risk. Significant bi-allelic effects were also observed for G396D and Y179C/G396D compound heterozygotes and a marginal mono-allelic effect for variant Y179C. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.

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

Last Updated: May 19, 2024