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NM_001048174.2(MUTYH):c.13C>T (p.Arg5Ter) AND Familial adenomatous polyposis 2

Germline classification:
Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:
Mar 25, 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:
RCV000206117.18

Allele description [Variation Report for NM_001048174.2(MUTYH):c.13C>T (p.Arg5Ter)]

NM_001048174.2(MUTYH):c.13C>T (p.Arg5Ter)

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.13C>T (p.Arg5Ter)
Other names:
p.R19*:CGA>TGA
HGVS:
  • NC_000001.11:g.45334493G>A
  • NG_008189.1:g.10978C>T
  • NM_001048171.2:c.13C>T
  • NM_001048172.2:c.13C>T
  • NM_001048173.2:c.13C>T
  • NM_001048174.2:c.13C>TMANE SELECT
  • NM_001128425.2:c.55C>T
  • NM_001293190.2:c.55C>T
  • NM_001293191.2:c.13C>T
  • NM_001293192.2:c.-200C>T
  • NM_001293195.2:c.13C>T
  • NM_001293196.2:c.-200C>T
  • NM_001350650.2:c.-259C>T
  • NM_001350651.2:c.-195C>T
  • NM_012222.3:c.55C>T
  • NP_001041636.2:p.Arg5Ter
  • NP_001041637.1:p.Arg5Ter
  • NP_001041638.1:p.Arg5Ter
  • NP_001041639.1:p.Arg5Ter
  • NP_001041639.1:p.Arg5Ter
  • NP_001121897.1:p.Arg19Ter
  • NP_001121897.1:p.Arg19Ter
  • NP_001280119.1:p.Arg19Ter
  • NP_001280120.1:p.Arg5Ter
  • NP_001280124.1:p.Arg5Ter
  • NP_036354.1:p.Arg19Ter
  • LRG_220t1:c.55C>T
  • LRG_220:g.10978C>T
  • LRG_220p1:p.Arg19Ter
  • NC_000001.10:g.45800165G>A
  • NM_001048174.1:c.13C>T
  • NM_001128425.1:c.55C>T
  • NR_146882.2:n.241C>T
  • NR_146883.2:n.164C>T
  • p.Arg19Stop
Protein change:
R19*
Links:
dbSNP: rs587780088
NCBI 1000 Genomes Browser:
rs587780088
Molecular consequence:
  • NM_001293192.2:c.-200C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001293196.2:c.-200C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350650.2:c.-259C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350651.2:c.-195C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NR_146882.2:n.241C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.164C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001048171.2:c.13C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048172.2:c.13C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048173.2:c.13C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048174.2:c.13C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001128425.2:c.55C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293190.2:c.55C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293191.2:c.13C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293195.2:c.13C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_012222.3:c.55C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

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
SCV000260463Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 21, 2024)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV004198918Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Jul 26, 2023)
unknownclinical testing

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

SCV004806382Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Mar 25, 2024)
germlineclinical testing

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

SCV004835737All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Jun 26, 2023)
germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical testing
not providedunknownunknownnot 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 (16)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000260463.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Arg19*) 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 (rs587780088, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with adenomatous polyposis and colorectal cancer (PMID: 19394335, 22641385, 24799981). ClinVar contains an entry for this variant (Variation ID: 127845). For these reasons, this variant has been classified as Pathogenic.

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

From Baylor Genetics, SCV004198918.1

#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 Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004806382.1

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

From All of Us Research Program, National Institutes of Health, SCV004835737.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (10)

Description

This variant changes 1 nucleotide in exon 2 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 the compound heterozygous state in an individual affected with MUTYH-associated polyposis (PMID: 32888815), in biallelic individuals affected with colorectal cancer (PMID: 19732775, 32973888), and in an individual with an unknown second allele affected with colorectal cancer (PMID: 33563768). This variant has also been reported in individuals affected with lung cancer (PMID: 35712480; Wu, et al. poster #230, AACR 2023), renal cell carcinoma (PMID: 33062672), breast cancer (PMID: 33901219), as well as in individuals that participated in genetic screening (PMID: 34428338, 34404389). This variant has been identified in 2/251478 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
1germlineunknown108544not providednot provided1not providednot providednot provided

Last Updated: Jan 19, 2025