NM_001128425.1(MUTYH):c.536A>G (p.Tyr179Cys) AND Endometrial carcinoma

Clinical significance:Pathogenic (Last evaluated: Dec 1, 2007)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000005613.2

Allele description [Variation Report for NM_001128425.1(MUTYH):c.536A>G (p.Tyr179Cys)]

NM_001128425.1(MUTYH):c.536A>G (p.Tyr179Cys)

Gene:
MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001128425.1(MUTYH):c.536A>G (p.Tyr179Cys)
Other names:
p.Y165C:TAC>TGC
HGVS:
  • NC_000001.11:g.45332803T>C
  • NG_008189.1:g.12668A>G
  • NM_001048171.1:c.494A>G
  • NM_001128425.1:c.536A>G
  • NM_001293192.1:c.176A>G
  • NP_001041636.1:p.Tyr165Cys
  • NP_001121897.1:p.Tyr179Cys
  • NP_001280121.1:p.Tyr59Cys
  • LRG_220t1:c.536A>G
  • LRG_220:g.12668A>G
  • LRG_220p1:p.Tyr179Cys
  • NC_000001.10:g.45798475T>C
Protein change:
Y165C; TYR165CYS
Links:
OMIM: 604933.0001; dbSNP: 34612342
GMAF:
0.0002(C), 34612342
NCBI 1000 Genomes Browser:
rs34612342
Allele Frequency:
0.00162(C), GO-ESP
Molecular consequence:
  • NM_001128425.1:c.536A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Endometrial carcinoma
Synonyms:
Endometrial carcinoma, somatic; Endometrial cancer, somatic; Endometrial cancer
Identifiers:
MedGen: C0476089; OMIM: 608089; Human Phenotype Ontology: HP:0012114

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000025795OMIMno assertion criteria providedPathogenic
(Dec 1, 2007)
unknownliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownnot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors.

Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, Hodges AK, Davies DR, David SS, Sampson JR, Cheadle JP.

Nat Genet. 2002 Feb;30(2):227-32. Epub 2002 Jan 30.

PubMed [citation]
PMID:
11818965

Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH.

Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP.

N Engl J Med. 2003 Feb 27;348(9):791-9.

PubMed [citation]
PMID:
12606733
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000025795.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

In a Welsh family in which 3 sibs had familial adenomatous polyposis-2 (FAP2; 608456), Al-Tassan et al. (2002) could find no clear germline pathogenic change in the APC gene. However, they showed that 11 tumors from the 3 affected sibs contained 18 somatic inactivating mutations of APC and that 15 of these mutations were G:C-T:A transversions--a significantly greater proportion than is found in sporadic tumors or in tumors associated with familial adenomatous polyposis. Analysis of the mutY gene showed that the affected sibs were compound heterozygous for 2 missense variants, tyr165 to cys (Y165C) and gly382 to asp (G382D; 604933.0002). Thus, defective base excision repair was implicated by these findings in predisposition to tumors in humans.

Sieber et al. (2003) found the germline Y165C mutation in homozygous or compound heterozygous state in 5 of 12 patients from the UK with multiple adenomas.

Barnetson et al. (2007) reported a patient with endometrial adenocarcinoma (see 608089) and sebaceous carcinoma of the face who was compound heterozygous for the Y165C and G382D mutations. Colonic adenomas were not reported, but a paternal aunt reportedly had colorectal cancer in her thirties. Barnetson et al. (2007) noted that the phenotype associated with biallelic MUTYH mutations may include extracolonic manifestations, including endometrial cancer and sebaceous carcinoma, as seen in other inherited colorectal cancer syndromes.

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

Last Updated: May 8, 2018