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NM_001048174.2(MUTYH):c.544C>T (p.Gln182Ter) AND Familial adenomatous polyposis 2

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Mar 5, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000554059.12

Allele description [Variation Report for NM_001048174.2(MUTYH):c.544C>T (p.Gln182Ter)]

NM_001048174.2(MUTYH):c.544C>T (p.Gln182Ter)

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.544C>T (p.Gln182Ter)
HGVS:
  • NC_000001.11:g.45332636G>A
  • NG_008189.1:g.12835C>T
  • NM_001048171.2:c.544C>T
  • NM_001048172.2:c.547C>T
  • NM_001048173.2:c.544C>T
  • NM_001048174.2:c.544C>TMANE SELECT
  • NM_001128425.2:c.628C>T
  • NM_001293190.2:c.589C>T
  • NM_001293191.2:c.577C>T
  • NM_001293192.2:c.268C>T
  • NM_001293195.2:c.544C>T
  • NM_001293196.2:c.268C>T
  • NM_001350650.2:c.199C>T
  • NM_001350651.2:c.199C>T
  • NM_012222.3:c.619C>T
  • NP_001041636.2:p.Gln182Ter
  • NP_001041637.1:p.Gln183Ter
  • NP_001041638.1:p.Gln182Ter
  • NP_001041639.1:p.Gln182Ter
  • NP_001121897.1:p.Gln210Ter
  • NP_001121897.1:p.Gln210Ter
  • NP_001280119.1:p.Gln197Ter
  • NP_001280120.1:p.Gln193Ter
  • NP_001280121.1:p.Gln90Ter
  • NP_001280124.1:p.Gln182Ter
  • NP_001280125.1:p.Gln90Ter
  • NP_001337579.1:p.Gln67Ter
  • NP_001337580.1:p.Gln67Ter
  • NP_036354.1:p.Gln207Ter
  • LRG_220t1:c.628C>T
  • LRG_220:g.12835C>T
  • LRG_220p1:p.Gln210Ter
  • NC_000001.10:g.45798308G>A
  • NM_001128425.1:c.628C>T
  • NR_146882.2:n.772C>T
  • NR_146883.2:n.621C>T
Protein change:
Q182*
Links:
dbSNP: rs376561094
NCBI 1000 Genomes Browser:
rs376561094
Molecular consequence:
  • NR_146882.2:n.772C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.621C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001048171.2:c.544C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048172.2:c.547C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048173.2:c.544C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048174.2:c.544C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001128425.2:c.628C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293190.2:c.589C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293191.2:c.577C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293192.2:c.268C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293195.2:c.544C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293196.2:c.268C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001350650.2:c.199C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001350651.2:c.199C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_012222.3:c.619C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
2

Condition(s)

Name:
Familial adenomatous polyposis 2
Synonyms:
COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE; ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE; MYH-associated polyposis; 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
SCV000639348Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Sep 10, 2023)
germlineclinical testing

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

SCV004841670All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Mar 5, 2024)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown2not providednot provided143475not 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 (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000639348.6

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

Description

This sequence change creates a premature translational stop signal (p.Gln210*) in the MUTYH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). This variant is present in population databases (rs376561094, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with MUTYH-associated polyposis (PMID: 16557584, 19732775). This variant is also known as Q196X. ClinVar contains an entry for this variant (Variation ID: 233460). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic.

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

From All of Us Research Program, National Institutes of Health, SCV004841670.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (4)

Description

This variant changes 1 nucleotide in exon 8 of the MUTYH gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with MUTYH-associated polyposis (MAP; PMID: 16557584, 19032956, 19732775). This variant has been identified in 1/251452 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of MUTYH function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown143475not providednot provided2not providednot providednot provided

Last Updated: Jan 13, 2025