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NM_001048174.2(MUTYH):c.420+19_420+31del AND not provided

Germline classification:
Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:
Oct 1, 2023
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:
RCV000679429.23

Allele description [Variation Report for NM_001048174.2(MUTYH):c.420+19_420+31del]

NM_001048174.2(MUTYH):c.420+19_420+31del

Gene:
MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001048174.2(MUTYH):c.420+19_420+31del
HGVS:
  • NC_000001.10:g.45798561_45798573delTATTTCCCCTACC
  • NC_000001.11:g.45332889_45332901del
  • NG_008189.1:g.12572_12584del
  • NM_001048171.2:c.420+19_420+31del
  • NM_001048172.2:c.423+19_423+31del
  • NM_001048173.2:c.420+19_420+31del
  • NM_001048174.2:c.420+19_420+31delMANE SELECT
  • NM_001128425.2:c.504+19_504+31del
  • NM_001293190.2:c.465+19_465+31del
  • NM_001293191.2:c.453+19_453+31del
  • NM_001293192.2:c.144+19_144+31del
  • NM_001293195.2:c.420+19_420+31del
  • NM_001293196.2:c.144+19_144+31del
  • NM_001350650.2:c.75+19_75+31del
  • NM_001350651.2:c.75+19_75+31del
  • NM_012222.3:c.495+19_495+31del
  • LRG_220t1:c.504+19_504+31del
  • LRG_220:g.12572_12584del
  • NC_000001.10:g.45798559_45798571del
  • NC_000001.10:g.45798561_45798573del
  • NC_000001.10:g.45798561_45798573del
  • NC_000001.10:g.45798561_45798573delTATTTCCCCTACC
  • NM_001048174.2:c.420+19_420+31del
  • NM_001128425.1:c.504+19_504+31del
  • NM_001128425.1:c.504+19_504+31del
  • NM_001128425.1:c.504+19_504+31delTAGGGGAAATAGG
  • NM_001128425.2:c.504+19_504+31del
Links:
dbSNP: rs781222233
NCBI 1000 Genomes Browser:
rs781222233
Molecular consequence:
  • NM_001048171.2:c.420+19_420+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001048172.2:c.423+19_423+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001048173.2:c.420+19_420+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001048174.2:c.420+19_420+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001128425.2:c.504+19_504+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293190.2:c.465+19_465+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293191.2:c.453+19_453+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293192.2:c.144+19_144+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293195.2:c.420+19_420+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293196.2:c.144+19_144+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001350650.2:c.75+19_75+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001350651.2:c.75+19_75+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_012222.3:c.495+19_495+31del - intron variant - [Sequence Ontology: SO:0001627]
Observations:
1

Condition(s)

Synonyms:
none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000806359PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Jan 8, 2018)
germlineclinical testing

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

SCV002506259ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)
Pathogenic
(Jan 25, 2022)
germlineclinical testing

Citation Link,

SCV004123769CeGaT Center for Human Genetics Tuebingen
criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)
Likely pathogenic
(Oct 1, 2023)
germlineclinical testing

Citation Link,

SCV005187351Clinical Genetics Laboratory, Skane University Hospital Lund
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Nov 28, 2022)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV000806359.1

#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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV002506259.2

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

Description

The MUTYH c.504+19_504+31del variant (rs781222233) is reported in the literature in the compound heterozygous or homozygous state in several individuals and families affected with MUTYH-associated polyposis (Di Gregorio 2006, Fostira 2010, Jones 2009, Morak 2010, Papp 2016, Vogt 2009). This variant is also reported in ClinVar (Variation ID: 406825), and is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This is an intronic variant that deleted 13 nucleotides of intron 6, and in vitro functional analyses demonstrate skipping of exon 6, leading to an in-frame deletion that removes part of the critical glycosylase catalytic domain (Fostira 2010). Based on available information, this variant is considered to be pathogenic. References: Di Gregorio C et al. Immunohistochemical expression of MYH protein can be used to identify patients with MYH-associated polyposis. Gastroenterology. 2006 Aug;131(2):439-44. PMID: 16890597. Fostira F et al. An in-frame exon-skipping MUTYH mutation is associated with early-onset colorectal cancer. Dis Colon Rectum. 2010 Aug;53(8):1197-201. PMID: 20628285. Jones N et al. Increased colorectal cancer incidence in obligate carriers of heterozygous mutations in MUTYH. Gastroenterology. 2009 Aug;137(2):489-94, 494.e1; quiz 725-6. PMID: 19394335. Morak M et al. MUTYH-associated polyposis - variability of the clinical phenotype in patients with biallelic and monoallelic MUTYH mutations and report on novel mutations. Clin Genet. 2010 Oct;78(4):353-63. PMID: 20618354. Papp J et al. Contribution of APC and MUTYH mutations to familial adenomatous polyposis susceptibility in Hungary. Fam Cancer. 2016 Jan;15(1):85-97. PMID: 26446593. Vogt S et al. Expanded extracolonic tumor spectrum in MUTYH-associated polyposis. Gastroenterology. 2009 Dec;137(6):1976-85.e1-10. PMID: 19732775.

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

From CeGaT Center for Human Genetics Tuebingen, SCV004123769.11

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

MUTYH: PM3:Strong, PM2, PS3:Supporting, PS4:Supporting

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005187351.1

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

Last Updated: Jan 13, 2025