NM_001128425.1(MUTYH):c.1438G>T (p.Glu480Ter) AND MYH-associated polyposis

Clinical significance:Pathogenic (Last evaluated: Mar 28, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000005618.5

Allele description [Variation Report for NM_001128425.1(MUTYH):c.1438G>T (p.Glu480Ter)]

NM_001128425.1(MUTYH):c.1438G>T (p.Glu480Ter)

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.1438G>T (p.Glu480Ter)
HGVS:
  • NC_000001.11:g.45331220C>A
  • NG_008189.1:g.14251G>T
  • NM_001128425.1:c.1438G>T
  • NP_001041636.1:p.Glu466Ter
  • NP_001121897.1:p.Glu480Ter
  • LRG_220t1:c.1438G>T
  • LRG_220:g.14251G>T
  • LRG_220p1:p.Glu480Ter
  • NC_000001.10:g.45796892C>A
Protein change:
E466*; GLU466TER
Links:
OMIM: 604933.0005; dbSNP: 121908381
GMAF:
0.0018(A), 121908381
NCBI 1000 Genomes Browser:
rs121908381
Molecular consequence:
  • NM_001128425.1:c.1438G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
MYH-associated polyposis (FAP2)
Synonyms:
COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE; ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE; FAP type 2
Identifiers:
MedGen: C1837991; Orphanet: 220460; OMIM: 608456
Age of onset:
Adult

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000025800OMIMno assertion criteria providedPathogenic
(Nov 1, 2002)
germlineliterature only

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

SCV000153903Invitaecriteria provided, single submitter
(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Mar 28, 2016)
germlineclinical testing

Citation Link,

SCV000246169GeneReviewsno assertion criteria providedPathogenic
(Sep 24, 2015)
germlineliterature only

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedliterature only
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, SCV000025800.2

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

Description

In 3 patients with multiple colorectal adenomas (FAP2; 608456) from unrelated Indian families, Jones et al. (2002) identified homozygosity for a 494A-G mutation in exon 14 of the MUTYH gene, resulting in a glu466-to-ter (E466X) substitution.

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

From Invitae, SCV000153903.2

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

Description

This sequence change creates a premature translational stop signal at codon 480 (p.Glu480*) of the MUTYH gene. It is expected to result in an absent or disrupted protein product. Truncating variants in MUTYH are known to be pathogenic. This particular truncation has been reported in the literature in individuals affected with MUTYH-associated polyposis syndrome. It is a frequent disease-causing variant in South Asian individuals with MUTYH-associated polyposis (PMID: 17369389, 12393807, 19732775, 19032956, 12853198, 17874208, 15635083). This variant is also known as c.1396G>T (p.Glu466X or E466X) in the literature. Experimental studies have shown that this nonsense change leads to reduced expression of a smaller, truncated MUTYH protein that is devoid of both glycosylase and DNA-binding activity (PMID: 18534194). For these reasons, this variant has been classified as Pathogenic.

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

From GeneReviews, SCV000246169.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature onlynot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 23, 2016