NM_001048174.2(MUTYH):c.1183G>T (p.Glu395Ter) AND Familial adenomatous polyposis 2

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Mar 29, 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:: RCV000462491.7

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1183G>T (p.Glu395Ter)]

NM_001048174.2(MUTYH):c.1183G>T (p.Glu395Ter)

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.1183G>T (p.Glu395Ter)

HGVS:

NC_000001.11:g.45331476C>A
NG_008189.1:g.13995G>T
NM_001048171.2:c.1183G>T
NM_001048172.2:c.1186G>T
NM_001048173.2:c.1183G>T
NM_001048174.2:c.1183G>TMANE SELECT
NM_001128425.2:c.1267G>T
NM_001293190.2:c.1228G>T
NM_001293191.2:c.1216G>T
NM_001293192.2:c.907G>T
NM_001293195.2:c.1183G>T
NM_001293196.2:c.907G>T
NM_001350650.2:c.838G>T
NM_001350651.2:c.838G>T
NM_012222.3:c.1258G>T
NP_001041636.2:p.Glu395Ter
NP_001041637.1:p.Glu396Ter
NP_001041638.1:p.Glu395Ter
NP_001041639.1:p.Glu395Ter
NP_001121897.1:p.Glu423Ter
NP_001121897.1:p.Glu423Ter
NP_001280119.1:p.Glu410Ter
NP_001280120.1:p.Glu406Ter
NP_001280121.1:p.Glu303Ter
NP_001280124.1:p.Glu395Ter
NP_001280125.1:p.Glu303Ter
NP_001337579.1:p.Glu280Ter
NP_001337580.1:p.Glu280Ter
NP_036354.1:p.Glu420Ter
LRG_220t1:c.1267G>T
LRG_220:g.13995G>T
LRG_220p1:p.Glu423Ter
NC_000001.10:g.45797148C>A
NM_001128425.1:c.1267G>T
NR_146882.2:n.1411G>T
NR_146883.2:n.1260G>T

Protein change:

E280*

Links:

dbSNP: rs1060501321

NCBI 1000 Genomes Browser:

rs1060501321

Molecular consequence:

NR_146882.2:n.1411G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1260G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001048171.2:c.1183G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001048172.2:c.1186G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001048173.2:c.1183G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001048174.2:c.1183G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001128425.2:c.1267G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293190.2:c.1228G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293191.2:c.1216G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293192.2:c.907G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293195.2:c.1183G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293196.2:c.907G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001350650.2:c.838G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001350651.2:c.838G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_012222.3:c.1258G>T - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000545712	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 29, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18534194, 20663686, 28492532
SCV004198981	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 9, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000545712

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 29, 2023)

germline

clinical testing

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

SCV004198981

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 9, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 (4)

Details of each submission

From Invitae, SCV000545712.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 406823). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu423*) 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).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004198981.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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