NM_001048174.2(MUTYH):c.383G>A (p.Trp128Ter) AND MYH-associated polyposis

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Dec 15, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000411443.8

Allele description [Variation Report for NM_001048174.2(MUTYH):c.383G>A (p.Trp128Ter)]

NM_001048174.2(MUTYH):c.383G>A (p.Trp128Ter)

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.383G>A (p.Trp128Ter)
HGVS:
  • NC_000001.11:g.45332955C>T
  • NG_008189.1:g.12516G>A
  • NM_001048171.1:c.425G>A
  • NM_001048171.2:c.383G>A
  • NM_001048172.2:c.386G>A
  • NM_001048173.2:c.383G>A
  • NM_001048174.2:c.383G>AMANE SELECT
  • NM_001128425.1:c.467G>A
  • NM_001128425.2:c.467G>A
  • NM_001293190.2:c.428G>A
  • NM_001293191.2:c.416G>A
  • NM_001293192.2:c.107G>A
  • NM_001293195.2:c.383G>A
  • NM_001293196.2:c.107G>A
  • NM_001350650.2:c.38G>A
  • NM_001350651.2:c.38G>A
  • NM_012222.3:c.458G>A
  • NP_001041636.1:p.Trp142Ter
  • NP_001041636.2:p.Trp128Ter
  • NP_001041637.1:p.Trp129Ter
  • NP_001041638.1:p.Trp128Ter
  • NP_001041639.1:p.Trp128Ter
  • NP_001121897.1:p.Trp156Ter
  • NP_001121897.1:p.Trp156Ter
  • NP_001280119.1:p.Trp143Ter
  • NP_001280120.1:p.Trp139Ter
  • NP_001280121.1:p.Trp36Ter
  • NP_001280124.1:p.Trp128Ter
  • NP_001280125.1:p.Trp36Ter
  • NP_001337579.1:p.Trp13Ter
  • NP_001337580.1:p.Trp13Ter
  • NP_036354.1:p.Trp153Ter
  • LRG_220t1:c.467G>A
  • LRG_220:g.12516G>A
  • LRG_220p1:p.Trp156Ter
  • NC_000001.10:g.45798627C>T
  • NC_000001.10:g.45798627C>T
  • NR_146882.2:n.611G>A
  • NR_146883.2:n.460G>A
  • p.Trp156*
Protein change:
W128*
Links:
dbSNP: rs762307622
NCBI 1000 Genomes Browser:
rs762307622
Molecular consequence:
  • NR_146882.2:n.611G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.460G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001048171.1:c.425G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048171.2:c.383G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048172.2:c.386G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048173.2:c.383G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048174.2:c.383G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001128425.1:c.467G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001128425.2:c.467G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293190.2:c.428G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293191.2:c.416G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293192.2:c.107G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293195.2:c.383G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293196.2:c.107G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001350650.2:c.38G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001350651.2:c.38G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_012222.3:c.458G>A - 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; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0012041; MedGen: C3272841; Orphanet: 220460; OMIM: 608456

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000487319Counsylcriteria provided, single submitter
Likely pathogenic
(Dec 13, 2015)
unknownclinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV000545719Invitaecriteria provided, single submitter
Pathogenic
(Aug 17, 2020)
germlineclinical testing

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

SCV001478129Department of Pediatrics,Memorial Sloan Kettering Cancer Centercriteria provided, single submitter
Pathogenic
(Dec 15, 2020)
germlineresearch

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedresearch
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Detection of inherited mutations for hereditary cancer using target enrichment and next generation sequencing.

Guan Y, Hu H, Peng Y, Gong Y, Yi Y, Shao L, Liu T, Li G, Wang R, Dai P, Bignon YJ, Xiao Z, Yang L, Mu F, Xiao L, Xie Z, Yan W, Xu N, Zhou D, Yi X.

Fam Cancer. 2015 Mar;14(1):9-18. doi: 10.1007/s10689-014-9749-9.

PubMed [citation]
PMID:
25151137

Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas.

Pilati C, Shinde J, Alexandrov LB, Assié G, André T, Hélias-Rodzewicz Z, Ducoudray R, Le Corre D, Zucman-Rossi J, Emile JF, Bertherat J, Letouzé E, Laurent-Puig P.

J Pathol. 2017 May;242(1):10-15. doi: 10.1002/path.4880. Epub 2017 Mar 29.

PubMed [citation]
PMID:
28127763
See all PubMed Citations (7)

Details of each submission

From Counsyl, SCV000487319.1

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

From Invitae, SCV000545719.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Trp156*) in the MUTYH gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs762307622, ExAC 0.06%). This variant has been reported in the literature in individuals affected with colorectal cancer (PMID: 25151137, 28127763). This variant is also known as c.425G>A (p.W142X) in the literature. ClinVar contains an entry for this variant (Variation ID: 230971). Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). For these reasons, this variant has been classified as Pathogenic.

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

From Department of Pediatrics,Memorial Sloan Kettering Cancer Center, SCV001478129.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 25, 2021

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