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NM_001048174.2(MUTYH):c.228C>A (p.Tyr76Ter) AND Carcinoma of colon

Germline classification:
Pathogenic (1 submission)
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:
RCV001353649.10

Allele description [Variation Report for NM_001048174.2(MUTYH):c.228C>A (p.Tyr76Ter)]

NM_001048174.2(MUTYH):c.228C>A (p.Tyr76Ter)

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.228C>A (p.Tyr76Ter)
HGVS:
  • NC_000001.11:g.45333449G>T
  • NG_008189.1:g.12022C>A
  • NM_001048171.2:c.228C>A
  • NM_001048172.2:c.231C>A
  • NM_001048173.2:c.228C>A
  • NM_001048174.2:c.228C>AMANE SELECT
  • NM_001128425.2:c.312C>A
  • NM_001293190.2:c.273C>A
  • NM_001293191.2:c.261C>A
  • NM_001293192.2:c.-49C>A
  • NM_001293195.2:c.228C>A
  • NM_001293196.2:c.-49C>A
  • NM_001350650.2:c.-44C>A
  • NM_001350651.2:c.-44C>A
  • NM_012222.3:c.303C>A
  • NP_001041636.1:p.Tyr90Ter
  • NP_001041636.2:p.Tyr76Ter
  • NP_001041637.1:p.Tyr77Ter
  • NP_001041638.1:p.Tyr76Ter
  • NP_001041639.1:p.Tyr76Ter
  • NP_001121897.1:p.Tyr104Ter
  • NP_001121897.1:p.Tyr104Ter
  • NP_001280119.1:p.Tyr91Ter
  • NP_001280120.1:p.Tyr87Ter
  • NP_001280124.1:p.Tyr76Ter
  • NP_036354.1:p.Tyr101Ter
  • LRG_220t1:c.312C>A
  • LRG_220:g.12022C>A
  • LRG_220p1:p.Tyr104Ter
  • NC_000001.10:g.45799121G>T
  • NM_001048171.1:c.270C>A
  • NM_001128425.1:c.312C>A
  • NR_146882.2:n.456C>A
  • NR_146883.2:n.379C>A
  • p.Tyr104*
  • p.Y104*
Protein change:
Y101*; TYR90TER
Links:
OMIM: 604933.0004; dbSNP: rs121908380
NCBI 1000 Genomes Browser:
rs121908380
Molecular consequence:
  • NM_001293192.2:c.-49C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001293196.2:c.-49C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350650.2:c.-44C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350651.2:c.-44C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NR_146882.2:n.456C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.379C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001048171.2:c.228C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048172.2:c.231C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048173.2:c.228C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048174.2:c.228C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001128425.2:c.312C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293190.2:c.273C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293191.2:c.261C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293195.2:c.228C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_012222.3:c.303C>A - nonsense - [Sequence Ontology: SO:0001587]
Observations:
3

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
SCV000592679Department 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 providedunknownyes3not providednot providednot providednot providedclinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000592679.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testingnot provided

Description

The MUTYH p.Tyr104X variant was identified in 12 of 622 proband chromosomes (frequency 0.019) from individuals or families with adenomatous polyposis and/or colorectal cancer (Croitoru 2007, Di Gregorio 2006, Jenkins 2006, O'Shea 2008, Ponti 2007, Vogt 2009). Two probands from these studies were identified as homozoygous carriers of the variant, while the remaining probands were compound heterozyous carriers of the variant with a second MUTYH variant. The variant was listed in dbSNP (ID: rs121908380) “With pathogenic allele” with a minor allele frequency of 0.001 (1000 Genomes Project), and was also identified in the HGMD, UMD (1X as a causal variant), and the “InSiGHT Colon Cancer Database”. The p.Tyr104X variant leads to a premature stop codon at position 104, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants in the MUTYH gene are an established mechanism of disease in MUTYH-associated polyposis. One functional study demonstrated an absence of both glycosylase and DNA binding activities for the variant (Ali 2008). 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 provided3not providednot providednot provided

Last Updated: Nov 10, 2024