NM_001048174.2(MUTYH):c.856C>T (p.Gln286Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 5, 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:: RCV000129103.10

Allele description [Variation Report for NM_001048174.2(MUTYH):c.856C>T (p.Gln286Ter)]

NM_001048174.2(MUTYH):c.856C>T (p.Gln286Ter)

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.856C>T (p.Gln286Ter)

HGVS:

NC_000001.11:g.45332080G>A
NG_008189.1:g.13391C>T
NM_001048171.2:c.856C>T
NM_001048172.2:c.859C>T
NM_001048173.2:c.856C>T
NM_001048174.2:c.856C>TMANE SELECT
NM_001128425.2:c.940C>T
NM_001293190.2:c.901C>T
NM_001293191.2:c.889C>T
NM_001293192.2:c.580C>T
NM_001293195.2:c.856C>T
NM_001293196.2:c.580C>T
NM_001350650.2:c.511C>T
NM_001350651.2:c.511C>T
NM_012222.3:c.931C>T
NP_001041636.2:p.Gln286Ter
NP_001041637.1:p.Gln287Ter
NP_001041638.1:p.Gln286Ter
NP_001041639.1:p.Gln286Ter
NP_001121897.1:p.Gln314Ter
NP_001121897.1:p.Gln314Ter
NP_001280119.1:p.Gln301Ter
NP_001280120.1:p.Gln297Ter
NP_001280121.1:p.Gln194Ter
NP_001280124.1:p.Gln286Ter
NP_001280125.1:p.Gln194Ter
NP_001337579.1:p.Gln171Ter
NP_001337580.1:p.Gln171Ter
NP_036354.1:p.Gln311Ter
LRG_220t1:c.940C>T
LRG_220:g.13391C>T
LRG_220p1:p.Gln314Ter
NC_000001.10:g.45797752G>A
NM_001128425.1:c.940C>T
NR_146882.2:n.1084C>T
NR_146883.2:n.933C>T
p.Q314*

Protein change:

Q171*

Links:

dbSNP: rs587781338

NCBI 1000 Genomes Browser:

rs587781338

Molecular consequence:

NR_146882.2:n.1084C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.933C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001048171.2:c.856C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001048172.2:c.859C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001048173.2:c.856C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001048174.2:c.856C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001128425.2:c.940C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293190.2:c.901C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293191.2:c.889C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293192.2:c.580C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293195.2:c.856C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293196.2:c.580C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001350650.2:c.511C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001350651.2:c.511C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_012222.3:c.931C>T - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000183814	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jan 5, 2024)	germline	clinical testing	Citation Link,
SCV001342789	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 15, 2020)	germline	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

SCV000183814

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jan 5, 2024)

germline

clinical testing

Citation Link,

SCV001342789

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 15, 2020)

germline

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

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 Ambry Genetics, SCV000183814.8

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

Description

The p.Q314* pathogenic mutation (also known as c.940C>T), located in exon 11 of the MUTYH gene, results from a C to T substitution at nucleotide position 940. This changes the amino acid from a glutamine to a stop codon within exon 11. This mutation has been reported in an individual with polyposis who also harbored the MUTYH p.Y179C mutation (Eliason K et al. J. Med. Genet. 2005 Jan;42(1):95-6). This mutation has also been reported in the heterozygous state in familial prostate cancer (Leongamornlert D et al. Br. J. Cancer 2014 Mar;110(6):1663-72). 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

From Color Diagnostics, LLC DBA Color Health, SCV001342789.2

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

Description

This variant changes 1 nucleotide in exon 11 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 identified in 3/251468 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.

#	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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