NM_001048174.2(MUTYH):c.1196_1205del (p.Trp399fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 2, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003352961.2

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1196_1205del (p.Trp399fs)]

NM_001048174.2(MUTYH):c.1196_1205del (p.Trp399fs)

Gene:

MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p34.1

Genomic location:

Preferred name:

NM_001048174.2(MUTYH):c.1196_1205del (p.Trp399fs)

HGVS:

NC_000001.11:g.45331454_45331463del
NG_008189.1:g.14008_14017del
NM_001048171.2:c.1196_1205del
NM_001048172.2:c.1199_1208del
NM_001048173.2:c.1196_1205del
NM_001048174.2:c.1196_1205delMANE SELECT
NM_001128425.1:c.1280_1289del10
NM_001128425.2:c.1280_1289del
NM_001293190.2:c.1241_1250del
NM_001293191.2:c.1229_1238del
NM_001293192.2:c.920_929del
NM_001293195.2:c.1196_1205del
NM_001293196.2:c.920_929del
NM_001350650.2:c.851_860del
NM_001350651.2:c.851_860del
NM_012222.3:c.1271_1280del
NP_001041636.2:p.Trp399fs
NP_001041637.1:p.Trp400fs
NP_001041638.1:p.Trp399fs
NP_001041639.1:p.Trp399fs
NP_001121897.1:p.Trp427fs
NP_001280119.1:p.Trp414fs
NP_001280120.1:p.Trp410fs
NP_001280121.1:p.Trp307fs
NP_001280124.1:p.Trp399fs
NP_001280125.1:p.Trp307fs
NP_001337579.1:p.Trp284fs
NP_001337580.1:p.Trp284fs
NP_036354.1:p.Trp424fs
LRG_220t1:c.1280_1289del10
LRG_220:g.14008_14017del
NC_000001.10:g.45797126_45797135del
NM_001128425.1:c.1280_1289delGGGCTGGGCC
NM_001128425.2:c.1280_1289del
NR_146882.2:n.1424_1433del
NR_146883.2:n.1273_1282del

Protein change:

W284fs

Links:

dbSNP: rs1553125677

NCBI 1000 Genomes Browser:

rs1553125677

Molecular consequence:

NM_001048171.2:c.1196_1205del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001048172.2:c.1199_1208del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001048173.2:c.1196_1205del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001048174.2:c.1196_1205del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001128425.2:c.1280_1289del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293190.2:c.1241_1250del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293191.2:c.1229_1238del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293192.2:c.920_929del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293195.2:c.1196_1205del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293196.2:c.920_929del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001350650.2:c.851_860del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001350651.2:c.851_860del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_012222.3:c.1271_1280del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_146882.2:n.1424_1433del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1273_1282del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004055766	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 2, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004055766

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 2, 2023)

germline

clinical testing

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

Citation Link

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

Citations

PubMed

Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer.

Pearlman R, Frankel WL, Swanson B, Zhao W, Yilmaz A, Miller K, Bacher J, Bigley C, Nelsen L, Goodfellow PJ, Goldberg RM, Paskett E, Shields PG, Freudenheim JL, Stanich PP, Lattimer I, Arnold M, Liyanarachchi S, Kalady M, Heald B, Greenwood C, Paquette I, et al.

JAMA Oncol. 2017 Apr 1;3(4):464-471. doi: 10.1001/jamaoncol.2016.5194.

PubMed [citation]

PMID:: 27978560
PMCID:: PMC5564179

Details of each submission

From Ambry Genetics, SCV004055766.2

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

Description

The c.1280_1289del10 pathogenic mutation, located in coding exon 13 of the MUTYH gene, results from a deletion of 10 nucleotides at nucleotide positions 1280 to 1289, causing a translational frameshift with a predicted alternate stop codon (p.W427Sfs*22). This alteration has been previously identified in an individual from a North American cohort of individuals with early onset colon cancer (Pearlman R et al. JAMA Oncol, 2017 Apr;3:464-471). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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

Last Updated: Sep 29, 2024

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