NM_001128425.1(MUTYH):c.312C>A (p.Tyr104Ter) AND MYH-associated polyposis

Clinical significance:Pathogenic (Last evaluated: Apr 24, 2015)

Review status:2 stars out of maximum of 4 stars

classified by multiple submitters

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000005617.3

Allele description [Variation Report for ]

NM_001128425.1(MUTYH):c.312C>A (p.Tyr104Ter)

Gene:
MUTYH:mutY homolog [Gene - OMIM]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001128425.1(MUTYH):c.312C>A (p.Tyr104Ter)
HGVS:
  • NC_000001.11:g.45333449G>T
  • NG_008189.1:g.12022C>A
  • NM_001128425.1:c.312C>A
  • NP_001121897.1:p.Tyr104Ter
  • LRG_220t1:c.312C>A
  • LRG_220:g.12022C>A
  • LRG_220p1:p.Tyr104Ter
  • NC_000001.10:g.45799121G>T
  • p.Y104*
Protein change:
Y90*; TYR90TER
Links:
OMIM: 604933.0004; dbSNP: 121908380
GMAF:
0.0006(A), 121908380
NCBI 1000 Genomes Browser:
rs121908380
Molecular consequence:
  • NM_001128425.1:c.312C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293192.1:c.-49C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]

Condition(s)

Name:
MYH-associated polyposis (FAP2)
Synonyms:
COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE; ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE; FAMILIAL ADENOMATOUS POLYPOSIS, 2; See all synonyms [MedGen]
Identifiers:
MedGen: C1837991; Orphanet: 220460; OMIM: 608456
Age of onset:
Adulthood

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Assertion and evidence details

Submission AccessionSubmitterReview StatusClinical Significance
(Last evaluated)
OriginMethodConsequenceCitations
SCV000025799OMIMPathogenic
(Apr 24, 2015)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000218794Invitaeclassified by single submitterPathogenic
(Nov 1, 2014)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations.

Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP.

Hum Mol Genet. 2002 Nov 1;11(23):2961-7.

PubMed [citation]
PMID:
12393807

Details of each submission

From OMIM, SCV000025799.2

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

Description

In a Pakistani patient with multiple colorectal adenomas (FAP2; 608456), Jones et al. (2002) identified homozygosity for a 270C-A mutation in exon 3 of the MUTYH gene, resulting in a tyr90-to-ter (Y90X) substitution.

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

From Invitae, SCV000218794.1

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

Description

This sequence change creates a premature translational stop signal at codon 104 (p.Tyr104*). It is expected to result in an absent or disrupted protein product. This sequence change has been reported in the literature and is present in population databases (rs121908380, 0.2% in CSAgilent European). This sequence change was reported in the homozygous state in 6 individuals from 3 families affected with MUTYH-associated polyposis syndrome (PMID: 12393807, 19732775). Experimental studies have shown that this nonsense change causes loss of MUTYH DNA-binding and repair activities in vitro (PMID: 18534194). This sequence change has been reported with the legacy name p.Tyr90* (PMID: 12393807, 18534194). For these reasons, this sequence change has been classified as Pathogenic.

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

Last Updated: Apr 27, 2015