NM_001048174.2(MUTYH):c.438G>A (p.Trp146Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 14, 2022
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:: RCV001023769.3

Allele description [Variation Report for NM_001048174.2(MUTYH):c.438G>A (p.Trp146Ter)]

NM_001048174.2(MUTYH):c.438G>A (p.Trp146Ter)

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.438G>A (p.Trp146Ter)

HGVS:

NC_000001.11:g.45332817C>T
NG_008189.1:g.12654G>A
NM_001048171.2:c.438G>A
NM_001048172.2:c.441G>A
NM_001048173.2:c.438G>A
NM_001048174.2:c.438G>AMANE SELECT
NM_001128425.2:c.522G>A
NM_001293190.2:c.483G>A
NM_001293191.2:c.471G>A
NM_001293192.2:c.162G>A
NM_001293195.2:c.438G>A
NM_001293196.2:c.162G>A
NM_001350650.2:c.93G>A
NM_001350651.2:c.93G>A
NM_012222.3:c.513G>A
NP_001041636.2:p.Trp146Ter
NP_001041637.1:p.Trp147Ter
NP_001041638.1:p.Trp146Ter
NP_001041639.1:p.Trp146Ter
NP_001121897.1:p.Trp174Ter
NP_001280119.1:p.Trp161Ter
NP_001280120.1:p.Trp157Ter
NP_001280121.1:p.Trp54Ter
NP_001280124.1:p.Trp146Ter
NP_001280125.1:p.Trp54Ter
NP_001337579.1:p.Trp31Ter
NP_001337580.1:p.Trp31Ter
NP_036354.1:p.Trp171Ter
LRG_220t1:c.522G>A
LRG_220:g.12654G>A
NC_000001.10:g.45798489C>T
NM_001128425.1:c.522G>A
NR_146882.2:n.666G>A
NR_146883.2:n.515G>A

Protein change:

W146*

Links:

dbSNP: rs1570423722

NCBI 1000 Genomes Browser:

rs1570423722

Molecular consequence:

NR_146882.2:n.666G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.515G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001048171.2:c.438G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001048172.2:c.441G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001048173.2:c.438G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001048174.2:c.438G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001128425.2:c.522G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001293190.2:c.483G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001293191.2:c.471G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001293192.2:c.162G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001293195.2:c.438G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001293196.2:c.162G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001350650.2:c.93G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001350651.2:c.93G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_012222.3:c.513G>A - nonsense - [Sequence Ontology: SO:0001587]

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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Nucleotide
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Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001185688	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 14, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16890597, 18091433 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001185688

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 14, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Immunohistochemical expression of MYH protein can be used to identify patients with MYH-associated polyposis.

Di Gregorio C, Frattini M, Maffei S, Ponti G, Losi L, Pedroni M, Venesio T, Bertario L, Varesco L, Risio M, Ponz de Leon M.

Gastroenterology. 2006 Aug;131(2):439-44.

PubMed [citation]

PMID:: 16890597

Heterogeneous molecular mechanisms underlie attenuated familial adenomatous polyposis.

Cattaneo F, Molatore S, Mihalatos M, Apessos A, Venesio T, Bione S, Grignani P, Nasioulas G, Ranzani GN.

Genet Med. 2007 Dec;9(12):836-41.

PubMed [citation]

PMID:: 18091433

Details of each submission

From Ambry Genetics, SCV001185688.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.W174* pathogenic mutation (also known as c.522G>A), located in coding exon 7 of the MUTYH gene, results from a G to A substitution at nucleotide position 522. This changes the amino acid from a tryptophan to a stop codon within coding exon 7. This alteration has been reported in a compound heterozygous state in a male patient with 100 tubulovillous adenomas of the ascending colon at age 35 (Di Gregorio C et al. Gastroenterology, 2006 Aug;131:439-44). This alteration has also been reported in a compound heterozygous state in a male patient with 30 colon polyps at age 35 (Cattaneo F et al. Genet. Med., 2007 Dec;9:836-41). 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: Oct 8, 2024

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