NM_001048174.2(MUTYH):c.228C>A (p.Tyr76Ter) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jul 31, 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:: RCV000486820.16

Allele description [Variation Report for NM_001048174.2(MUTYH):c.228C>A (p.Tyr76Ter)]

NM_001048174.2(MUTYH):c.228C>A (p.Tyr76Ter)

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.228C>A (p.Tyr76Ter)

HGVS:

NC_000001.11:g.45333449G>T
NG_008189.1:g.12022C>A
NM_001048171.2:c.228C>A
NM_001048172.2:c.231C>A
NM_001048173.2:c.228C>A
NM_001048174.2:c.228C>AMANE SELECT
NM_001128425.2:c.312C>A
NM_001293190.2:c.273C>A
NM_001293191.2:c.261C>A
NM_001293192.2:c.-49C>A
NM_001293195.2:c.228C>A
NM_001293196.2:c.-49C>A
NM_001350650.2:c.-44C>A
NM_001350651.2:c.-44C>A
NM_012222.3:c.303C>A
NP_001041636.1:p.Tyr90Ter
NP_001041636.2:p.Tyr76Ter
NP_001041637.1:p.Tyr77Ter
NP_001041638.1:p.Tyr76Ter
NP_001041639.1:p.Tyr76Ter
NP_001121897.1:p.Tyr104Ter
NP_001121897.1:p.Tyr104Ter
NP_001280119.1:p.Tyr91Ter
NP_001280120.1:p.Tyr87Ter
NP_001280124.1:p.Tyr76Ter
NP_036354.1:p.Tyr101Ter
LRG_220t1:c.312C>A
LRG_220:g.12022C>A
LRG_220p1:p.Tyr104Ter
NC_000001.10:g.45799121G>T
NM_001048171.1:c.270C>A
NM_001128425.1:c.312C>A
NR_146882.2:n.456C>A
NR_146883.2:n.379C>A
p.Tyr104*
p.Y104*

Protein change:

Y101*; TYR90TER

Links:

OMIM: 604933.0004; dbSNP: rs121908380

NCBI 1000 Genomes Browser:

rs121908380

Molecular consequence:

NM_001293192.2:c.-49C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001293196.2:c.-49C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350650.2:c.-44C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350651.2:c.-44C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NR_146882.2:n.456C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.379C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001048171.2:c.228C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001048172.2:c.231C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001048173.2:c.228C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001048174.2:c.228C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001128425.2:c.312C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001293190.2:c.273C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001293191.2:c.261C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001293195.2:c.228C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_012222.3:c.303C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000567387	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 4, 2022)	germline	clinical testing	Citation Link,
SCV001134474	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jan 20, 2019)	germline	clinical testing	PubMed (13) [See all records that cite these PMIDs] 12393807, 19732775, 24444654, 18534194, 17219385, 18091433, 27829682, 19279422, 18564191, 17273161, 22976915, 27705013, 26467025
SCV005090676	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 31, 2024)	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

SCV000567387

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jan 4, 2022)

germline

clinical testing

Citation Link,

SCV001134474

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Jan 20, 2019)

germline

clinical testing

PubMed (13)
[See all records that cite these PMIDs]

SCV005090676

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 31, 2024)

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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations.

Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP.

Hum Mol Genet. 2002 Nov 1;11(23):2961-7.

PubMed [citation]

PMID:: 12393807

Expanded extracolonic tumor spectrum in MUTYH-associated polyposis.

Vogt S, Jones N, Christian D, Engel C, Nielsen M, Kaufmann A, Steinke V, Vasen HF, Propping P, Sampson JR, Hes FJ, Aretz S.

Gastroenterology. 2009 Dec;137(6):1976-85.e1-10. doi: 10.1053/j.gastro.2009.08.052. Epub 2009 Sep 2.

PubMed [citation]

PMID:: 19732775

See all PubMed Citations (14)

Details of each submission

From GeneDx, SCV000567387.6

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed multiple times in the homozygous or compound heterozygous state in unrelated patients with adenomatous polyposis and/or colorectal cancer (Jones 2002, Croitoru 2004, Gismondi 2004, Croitoru 2007, Cattaneo 2007, Win 2014, Ricci 2017); Published functional studies demonstrate a damaging effect: abrogates glycosylase and DNA binding activities (Ali 2008); This variant is associated with the following publications: (PMID: 27631816, 18534194, 17273161, 19732775, 12393807, 17219385, 15523092, 14999774, 18091433, 27829682, 27194394, 25525159, 28381238, 24444654, 27705013, 28152038, 16492921, 23035301, 18564191, 16890597, 31589614, 33194656, 32012241, Ceylan2021[CaseReport], 34704405)

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001134474.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (13)

Description

The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in multiple symptomatic patients, and found in general population data that is consistent with pathogenicity. Occurs in multiple cases with a recessive pathogenic variant in the same gene. Assessment of experimental evidence suggests this variant results in abnormal protein function.

#	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 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV005090676.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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