NM_012222.2(MUTYH):c.499del (p.Glu166_Val167insTer) AND MYH-associated polyposis

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jun 6, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001206070.3

Allele description [Variation Report for NM_012222.2(MUTYH):c.499del (p.Glu166_Val167insTer)]

NM_012222.2(MUTYH):c.499del (p.Glu166_Val167insTer)

Gene:
MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_012222.2(MUTYH):c.499del (p.Glu166_Val167insTer)
HGVS:
  • NC_000001.11:g.45332832del
  • NG_008189.1:g.12640del
  • NM_001048171.1:c.466del
  • NM_001048172.1:c.427del
  • NM_001048173.1:c.424del
  • NM_001048174.1:c.424del
  • NM_001128425.1:c.508del
  • NM_001293190.1:c.469del
  • NM_001293191.1:c.457del
  • NM_001293192.1:c.148del
  • NM_001293195.1:c.424del
  • NM_001293196.1:c.148del
  • NM_001350650.1:c.79del
  • NM_001350651.1:c.79del
  • NM_012222.2:c.499del
  • NP_001041636.1:p.Glu155_Val156insTer
  • NP_001041637.1:p.Glu142_Val143insTer
  • NP_001041638.1:p.Glu141_Val142insTer
  • NP_001041639.1:p.Glu141_Val142insTer
  • NP_001121897.1:p.Glu169_Val170insTer
  • NP_001280119.1:p.Glu156_Val157insTer
  • NP_001280120.1:p.Glu152_Val153insTer
  • NP_001280121.1:p.Glu49_Val50insTer
  • NP_001280124.1:p.Glu141_Val142insTer
  • NP_001280125.1:p.Glu49_Val50insTer
  • NP_001337579.1:p.Glu26_Val27insTer
  • NP_001337580.1:p.Glu26_Val27insTer
  • NP_036354.1:p.Glu166_Val167insTer
  • LRG_220t1:c.508del
  • LRG_220:g.12640del
  • LRG_220p1:p.Glu169_Val170insTer
  • NC_000001.10:g.45798503del
  • NC_000001.10:g.45798504del
  • NM_001128425.1:c.508delG
  • NR_146882.1:n.682del
  • NR_146883.1:n.496del
Links:
dbSNP: rs1553129062
NCBI 1000 Genomes Browser:
rs1553129062
Molecular consequence:
  • NR_146882.1:n.682del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.1:n.496del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001048171.1:c.466del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048172.1:c.427del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048173.1:c.424del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048174.1:c.424del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001128425.1:c.508del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293190.1:c.469del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293191.1:c.457del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293192.1:c.148del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293195.1:c.424del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293196.1:c.148del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001350650.1:c.79del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001350651.1:c.79del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_012222.2:c.499del - 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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000697699Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Apr 13, 2017)
germlineclinical testing

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV001377358Invitaecriteria provided, single submitter
Pathogenic
(Jun 6, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Characterization of mutant MUTYH proteins associated with familial colorectal cancer.

Ali M, Kim H, Cleary S, Cupples C, Gallinger S, Bristow R.

Gastroenterology. 2008 Aug;135(2):499-507. doi: 10.1053/j.gastro.2008.04.035. Epub 2008 May 7.

PubMed [citation]
PMID:
18534194
PMCID:
PMC2761659

MUTYH-associated polyposis (MAP).

Nielsen M, Morreau H, Vasen HF, Hes FJ.

Crit Rev Oncol Hematol. 2011 Jul;79(1):1-16. doi: 10.1016/j.critrevonc.2010.05.011. Epub 2010 Jul 21. Review.

PubMed [citation]
PMID:
20663686
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697699.1

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

Description

Variant summary: The MUTYH c.508delG (p.Val170X) variant results in a premature termination codon, predicted to cause a truncated or absent MUTYH protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.1227_1228dupGG, p.Glu410fsX43). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121382 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.

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

From Invitae, SCV001377358.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Val170*) in the MUTYH gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 496103). 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

Last Updated: Jun 25, 2021

Support Center