ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.1087C>T (p.Gln363Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001048174.2(MUTYH):c.1087C>T (p.Gln363Ter)
Variation ID: 156509 Accession: VCV000156509.42
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p34.1 1: 45331676 (GRCh38) [ NCBI UCSC ] 1: 45797348 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 20, 2014 Feb 28, 2024 Oct 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001048174.2:c.1087C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001041639.1:p.Gln363Ter nonsense NM_001128425.2:c.1171C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Gln391Ter nonsense NM_001048171.2:c.1087C>T NP_001041636.2:p.Gln363Ter nonsense NM_001048172.2:c.1090C>T NP_001041637.1:p.Gln364Ter nonsense NM_001048173.2:c.1087C>T NP_001041638.1:p.Gln363Ter nonsense NM_001293190.2:c.1132C>T NP_001280119.1:p.Gln378Ter nonsense NM_001293191.2:c.1120C>T NP_001280120.1:p.Gln374Ter nonsense NM_001293192.2:c.811C>T NP_001280121.1:p.Gln271Ter nonsense NM_001293195.2:c.1087C>T NP_001280124.1:p.Gln363Ter nonsense NM_001293196.2:c.811C>T NP_001280125.1:p.Gln271Ter nonsense NM_001350650.2:c.742C>T NP_001337579.1:p.Gln248Ter nonsense NM_001350651.2:c.742C>T NP_001337580.1:p.Gln248Ter nonsense NM_012222.3:c.1162C>T NP_036354.1:p.Gln388Ter nonsense NR_146882.2:n.1315C>T non-coding transcript variant NR_146883.2:n.1164C>T non-coding transcript variant NC_000001.11:g.45331676G>A NC_000001.10:g.45797348G>A NG_008189.1:g.13795C>T LRG_220:g.13795C>T LRG_220t1:c.1171C>T LRG_220p1:p.Gln391Ter - Protein change
- Q391*, Q377*, Q271*, Q364*, Q374*, Q378*, Q388*, Q363*, Q248*
- Other names
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- Canonical SPDI
- NC_000001.11:45331675:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MUTYH | - | - |
GRCh38 GRCh37 |
2566 | 2714 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (2) |
no assertion criteria provided
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Jul 24, 2014 | RCV000144635.3 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Aug 6, 2018 | RCV000413062.8 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Oct 10, 2023 | RCV000410310.17 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Nov 16, 2022 | RCV000569738.9 | |
Pathogenic (1) |
no assertion criteria provided
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Aug 19, 2021 | RCV001572626.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 10, 2022 | RCV002221498.3 | |
Pathogenic (1) |
no assertion criteria provided
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Jul 1, 2021 | RCV003162600.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Aug 06, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000490628.2
First in ClinVar: Jan 09, 2017 Last updated: Apr 17, 2019 |
Comment:
This variant is denoted MUTYH c.1171C>T at the cDNA level and p.Gln391Ter (Q391X) at the protein level. The substitution creates a nonsense variant, which changes … (more)
This variant is denoted MUTYH c.1171C>T at the cDNA level and p.Gln391Ter (Q391X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also reported as MUTYH Gln377Ter using an alternate reference sequence (NM_001048171.1), has been reported in the homozygous or compound heterozygous state in several individuals with multiple adenomatous polyps and/or colorectal cancer (Nielsen 2005, Aretz 2006, Croitoru 2007, Cleary 2009), and functional studies by Ali et. al. (2008) demonstrated severely defective glycosylase and DNA binding activities. Based on currently available evidence, we consider MUTYH Gln391Ter to be pathogenic. (less)
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Pathogenic
(Jan 09, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: yes
Allele origin:
germline
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GeneKor MSA
Accession: SCV001950432.1
First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(Apr 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial colorectal cancer
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002498799.1
First in ClinVar: Apr 16, 2022 Last updated: Apr 16, 2022 |
Comment:
The c.1171C>T;p.(Gln391*) variant creates a premature translational stop signal in the MUTYH gene. It is expected to result in an absent or disrupted protein product … (more)
The c.1171C>T;p.(Gln391*) variant creates a premature translational stop signal in the MUTYH gene. It is expected to result in an absent or disrupted protein product -PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 156509; PMID: 16140997; PMID: 19732775; PMID: 24444654; PMID: 18534194; PMID: 20663686; PMID: 16557584; PMID: 17219385) - PS4. The variant is present at low allele frequencies population databases (rs587783057 – gnomAD 0.0001202%; ABraOM no frequency - http://abraom.ib.usp.br) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Brazil
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Pathogenic
(Oct 11, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000670131.4
First in ClinVar: Jan 01, 2018 Last updated: Nov 29, 2022 |
Comment:
The p.Q391* pathogenic mutation (also known as c.1171C>T), located in coding exon 12 of the MUTYH gene, results from a C to T substitution at … (more)
The p.Q391* pathogenic mutation (also known as c.1171C>T), located in coding exon 12 of the MUTYH gene, results from a C to T substitution at nucleotide position 1171. This changes the amino acid from a glutamine to a stop codon within coding exon 12. This alteration has been previously described in several individuals with attenuated polyposis and/or colon cancer in homozygous state or in conjugation with another pathogenic mutation (Nielsen M et al. J. Med. Genet. 2005 42(9):e54; Croitoru M et al. J. Surg. Oncol. 2007; 95(6):499-506; Olschwang S et al. Genet. Test. 2007; 11(3):315-20; Jones N et al. Gastroenterology 2009; 137(2):489-94, 494.e1; Vogt S et al. Gastroenterology 2009; 137(6):1976-85.e1-10; Ricci MT et al. J. Hum. Genet., 2017 Feb;62:309-315; Aretz S et al. Int J Cancer 2006 Aug;119(4):807-14). In addition, this mutation is also designated as Q377X in published literature. 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. (less)
Number of individuals with the variant: 1
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Pathogenic
(Jul 02, 2018)
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criteria provided, single submitter
Method: clinical testing
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MYH-associated polyposis
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV000837752.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
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Pathogenic
(Jun 08, 2016)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000487361.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
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Pathogenic
(Apr 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004198966.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Mar 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003820311.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Oct 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000545766.10
First in ClinVar: Jan 06, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln391*) in the MUTYH gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln391*) 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). This variant is present in population databases (rs587783057, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with MUTYH-associated polyposis (PMID: 16140997, 19732775, 24444654). This variant is also known as c.1129C>T (p.Q377X). ClinVar contains an entry for this variant (Variation ID: 156509). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 24, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888297.2
First in ClinVar: Jan 09, 2017 Last updated: Jan 01, 2022 |
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Pathogenic
(Nov 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000685548.4
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant changes 1 nucleotide in exon 12 of the MUTYH gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 12 of the MUTYH gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with colorectal polyposis and/or cancer in the homozygous or compound heterozygous state with another pathogenic variant (PMID: 16140997, 18564191, 19732775, 24444654, 27829682). This variant has been identified in 3/249660 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. (less)
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Pathogenic
(Jul 24, 2014)
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no assertion criteria provided
Method: clinical testing
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Carcinoma of colon
Affected status: unknown
Allele origin:
germline
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Pathway Genomics
Accession: SCV000189962.1
First in ClinVar: Oct 20, 2014 Last updated: Oct 20, 2014 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Carcinoma of colon
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001553370.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The MUTYH p.Gln391X variant was identified in 4 of 1188 proband chromosomes (frequency: 0.003) from individuals or families with colorectal cancer (Jones 2009, Vogt 2009, … (more)
The MUTYH p.Gln391X variant was identified in 4 of 1188 proband chromosomes (frequency: 0.003) from individuals or families with colorectal cancer (Jones 2009, Vogt 2009, Win 2011). The variant was also identified in dbSNP (ID: rs587783057) as With Pathogenic allele, ClinVar (classified as pathogenic by Counsyl, GeneDx, Invitae, Pathway Genomics), Clinvitae (classified as pathogenic by ClinVar, Invitae (alias c.1129C>T)), UMD-LSDB (22X causal), Insight Colon Cancer Gene Variant Database (classified as probably pathogenic), databases. The variant was not identified in Genesight-COGR, databases. The variant was identified in control databases in 4 of 245576 chromosomes at a frequency of 0.000016 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include EuropeanNon-Finnish in 4 of 111460 chromosomes (freq: 0.000036), while the variant was not observed in the African, Other, Latino, AshkenaziJewish, EastAsian, EuropeanFinnish, and SouthAsian populations. The c.1171C>T variant leads to a premature stop codon at position 391 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the MUTYH gene are an established mechanism of disease in MUTYH-associated polyposis and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
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Pathogenic
(Aug 19, 2021)
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no assertion criteria provided
Method: clinical testing
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Breast carcinoma
Affected status: yes
Allele origin:
germline
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Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences
Accession: SCV001792255.1
First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
Comment:
Invasive Ductal Carcinoma Estrogen Receptor: Positive Progesterone Receptor: Positive HER2 Receptor: Negative
Age: 50-59 years
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799792.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001955530.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(Jul 01, 2021)
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no assertion criteria provided
Method: research
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Gastric cancer
Affected status: unknown
Allele origin:
germline
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Laboratory for Genotyping Development, RIKEN
Accession: SCV002758515.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. | Usui Y | The New England journal of medicine | 2023 | PMID: 36988593 |
Type and frequency of MUTYH variants in Italian patients with suspected MAP: a retrospective multicenter study. | Ricci MT | Journal of human genetics | 2017 | PMID: 27829682 |
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer. | Win AK | Gastroenterology | 2014 | PMID: 24444654 |
MUTYH associated polyposis coli: one common and one rare mutation. | De Schepper HU | Digestive diseases and sciences | 2012 | PMID: 22402879 |
MUTYH-associated polyposis (MAP). | Nielsen M | Critical reviews in oncology/hematology | 2011 | PMID: 20663686 |
Expanded extracolonic tumor spectrum in MUTYH-associated polyposis. | Vogt S | Gastroenterology | 2009 | PMID: 19732775 |
Molecular analysis of the APC and MUTYH genes in Galician and Catalonian FAP families: a different spectrum of mutations? | Gómez-Fernández N | BMC medical genetics | 2009 | PMID: 19531215 |
Germline MutY human homologue mutations and colorectal cancer: a multisite case-control study. | Cleary SP | Gastroenterology | 2009 | PMID: 19245865 |
Pathological features of colorectal carcinomas in MYH-associated polyposis. | O'Shea AM | Histopathology | 2008 | PMID: 18564191 |
Characterization of mutant MUTYH proteins associated with familial colorectal cancer. | Ali M | Gastroenterology | 2008 | PMID: 18534194 |
Similar colorectal cancer risk in patients with monoallelic and biallelic mutations in the MYH gene identified in a population with adenomatous polyposis. | Olschwang S | Genetic testing | 2007 | PMID: 17949294 |
Germline MYH mutations in a clinic-based series of Canadian multiple colorectal adenoma patients. | Croitoru ME | Journal of surgical oncology | 2007 | PMID: 17219385 |
MUTYH-associated polyposis: 70 of 71 patients with biallelic mutations present with an attenuated or atypical phenotype. | Aretz S | International journal of cancer | 2006 | PMID: 16557584 |
Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP). | Nielsen M | Journal of medical genetics | 2005 | PMID: 16140997 |
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Text-mined citations for rs587783057 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.