ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.452A>G (p.Tyr151Cys)
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
-
NM_001048174.2(MUTYH):c.452A>G (p.Tyr151Cys)
Variation ID: 5293 Accession: VCV000005293.114
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p34.1 1: 45332803 (GRCh38) [ NCBI UCSC ] 1: 45798475 (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 Apr 4, 2013 May 1, 2024 Feb 16, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001048174.2:c.452A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001041639.1:p.Tyr151Cys missense NM_001128425.2:c.536A>G MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Tyr179Cys missense NM_001048171.2:c.452A>G NP_001041636.2:p.Tyr151Cys missense NM_001048172.2:c.455A>G NP_001041637.1:p.Tyr152Cys missense NM_001048173.2:c.452A>G NP_001041638.1:p.Tyr151Cys missense NM_001048174.1:c.452A>G NM_001293190.2:c.497A>G NP_001280119.1:p.Tyr166Cys missense NM_001293191.2:c.485A>G NP_001280120.1:p.Tyr162Cys missense NM_001293192.2:c.176A>G NP_001280121.1:p.Tyr59Cys missense NM_001293195.2:c.452A>G NP_001280124.1:p.Tyr151Cys missense NM_001293196.2:c.176A>G NP_001280125.1:p.Tyr59Cys missense NM_001350650.2:c.107A>G NP_001337579.1:p.Tyr36Cys missense NM_001350651.2:c.107A>G NP_001337580.1:p.Tyr36Cys missense NM_012222.3:c.527A>G NP_036354.1:p.Tyr176Cys missense NR_146882.2:n.680A>G non-coding transcript variant NR_146883.2:n.529A>G non-coding transcript variant NC_000001.11:g.45332803T>C NC_000001.10:g.45798475T>C NG_008189.1:g.12668A>G LRG_220:g.12668A>G LRG_220t1:c.536A>G LRG_220p1:p.Tyr179Cys - Protein change
- Y165C, Y179C, Y59C, Y176C, Y151C, Y162C, Y36C, Y152C, Y166C
- Other names
- p.Y165C:TAC>TGC
- Canonical SPDI
- NC_000001.11:45332802:T:C
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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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0.00020 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00135
The Genome Aggregation Database (gnomAD), exomes 0.00154
Exome Aggregation Consortium (ExAC) 0.00162
The Genome Aggregation Database (gnomAD) 0.00168
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
Help
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 |
2643 | 2796 |
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/Likely pathogenic (29) |
criteria provided, multiple submitters, no conflicts
|
Feb 5, 2024 | RCV000005612.66 | |
Pathogenic (1) |
no assertion criteria provided
|
Dec 1, 2007 | RCV000005613.10 | |
Pathogenic (19) |
criteria provided, multiple submitters, no conflicts
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Feb 6, 2024 | RCV000079502.70 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Feb 16, 2024 | RCV000115766.30 | |
not provided (1) |
no classification provided
|
Sep 19, 2013 | RCV000121607.12 | |
Pathogenic (2) |
no assertion criteria provided
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Jul 24, 2014 | RCV000144631.10 | |
Likely pathogenic (1) |
no assertion criteria provided
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Aug 7, 2021 | RCV001554314.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 15, 2022 | RCV002476933.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 7, 2023 | RCV003389663.5 |
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
(Jun 25, 2015)
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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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Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000257796.2
First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015 |
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Pathogenic
(Nov 20, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: yes
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV000266097.1
First in ClinVar: Mar 20, 2016 Last updated: Mar 20, 2016 |
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
colon cancer (present) , ovarian cancer (present)
Age: 50-59 years
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
colon cancer (present)
Age: 50-59 years
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
colon cancer (present) , skin cancer (present) , prostate cancer (present)
Age: 30-39 years
|
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Pathogenic
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
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MYH-Associated Polyposis
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000357903.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Comment:
Several studies describe the c.494A>G (p.Tyr165Cys) as a common pathogenic variant, also referred to as c.536A>G (p.Tyr179Cys) in the literature. In 2002, Al-Tassan et al. … (more)
Several studies describe the c.494A>G (p.Tyr165Cys) as a common pathogenic variant, also referred to as c.536A>G (p.Tyr179Cys) in the literature. In 2002, Al-Tassan et al. described a family with three siblings with multiple colorectal adenomas and carcinoma, found to be compound heterozygous for the p.Tyr165Cys variant. Four unaffected siblings were all heterozygous for a single variant or homozygous wild-type. Nielson et al. (2005) identified the p.Tyr165Cys variant in a presumed compound heterozygous state in 13 individuals and in a homozygous state in 14 individuals, out of 170 patients with polyposis who previously tested negative for APC mutations. The p.Tyr165Cys variant was the most common variant identified in the study cohort. Control data are unavailable for the p.Tyr165Cys variant which is reported at a frequency of 0.00302 in the European American population of the Exome Sequencing Project. In 2009, Nielsen et al. assessed genotype phenotype relationships of the common p.Tyr165Cys and p.Gly396Asp variants. Patients homozygous for the p.Tyr165Cys variant had a significantly increased chance of developing colorectal cancer compared to patients homozygous for the p.Gly396Asp variant or compound heterozygous for the p.Tyr165Cys and Gly382Asp variants (Nielsen et al. 2009). Ali et al. (2008) demonstrated significantly impaired DNA glycosylase and binding activities of the p.Tyr165Cys variant via in vitro functional assays, which were unable to generate any detectable cleavage products or to bind to the substrates. Similarly, Goto et al. (2010) demonstrated the adenine DNA glycosylase activity of the p. p.Tyr165Cys protein was 4.5% of wild-type. The collective evidence supports p.Tyr165Cys as a pathogenic variant. (less)
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Pathogenic
(Apr 02, 2020)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: yes
Allele origin:
germline
|
Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499743.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
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Pathogenic
(Jan 11, 2022)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV002070483.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
Comment:
DNA sequence analysis of the MUTYH gene demonstrated a sequence change, c.536A>G, in exon 7 that results in an amino acid change, p.Tyr179Cys. This pathogenic … (more)
DNA sequence analysis of the MUTYH gene demonstrated a sequence change, c.536A>G, in exon 7 that results in an amino acid change, p.Tyr179Cys. This pathogenic sequence change is a known founder mutation in the European population and has been described in the gnomAD database with a frequency of 0.25% in the non-Finnish European population (dbSNP rs34612342). This pathogenic sequence change has previously been described in the homozygous or compound heterozygous state in multiple patients with MUTYH-associated polyposis (PMIDs: 19032956, 11818965; Cleary et al., 2009). Multiple in vitro studies have supported the pathogenic nature of the p.Tyr179Cys change (PMIDs: 24569162, 25820570). The p.Tyr179Cys change affects a highly conserved amino acid residue located in a domain of the MUTYH protein that is known to be functional. The p.Tyr179Cys substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). (less)
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Pathogenic
(Aug 31, 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
|
St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Accession: SCV002584602.1
First in ClinVar: Oct 22, 2022 Last updated: Oct 22, 2022 |
Comment:
The MUTYH c.536A>G (p.Tyr179Cys) is a well-established pathogenic founder mutation for MUTYH-associated polyposis in the European population (PMID: 23035301, 23361220). This variant has been reported … (more)
The MUTYH c.536A>G (p.Tyr179Cys) is a well-established pathogenic founder mutation for MUTYH-associated polyposis in the European population (PMID: 23035301, 23361220). This variant has been reported to co-segregate with disease in individuals affected with colorectal cancer and polyposis (with polyp numbers ranging from 10 to >100) (PMID: 11818965, 12606733, 16557584, 19032956, 19732775, 27829682). Although MUTYH-associated polyposis is typically caused by biallelic variants affecting the MUTYH gene, there is evidence that monoallelic pathogenic MUTYH variants including this particular variant are associated with increased risk of colon cancer (PMID: 16492921, 19394335, 21063410, 24444654). This variant has a maximum subpopulation frequency of 0.25% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a deleterious effect on protein function, and functional studies have shown that this missense change disrupts MUTYH protein function (PMID: 18534194, 19836313, 19953527, 20418187, 20848659, 22926731, 23108399, 24569162, 25820570). This variant is also known as p.Tyr165Cys in the literature. In summary, this variant meets criteria to be classified as pathogenic. (less)
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Pathogenic
(Sep 20, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
Affected status: yes
Allele origin:
germline
|
Human Genetics Bochum, Ruhr University Bochum
Accession: SCV002758570.1
First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022 |
Comment:
ACMG criteria used to clasify this variant: PS3, PS4, PP3, PP1
|
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Pathogenic
(Apr 28, 2023)
|
criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: no
Allele origin:
germline
|
Institute of Human Genetics, Heidelberg University
Accession: SCV003936060.1
First in ClinVar: Jul 01, 2023 Last updated: Jul 01, 2023 |
Sex: male
|
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Pathogenic
(Nov 30, 2021)
|
criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: yes
Allele origin:
germline
|
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Accession: SCV002512305.2
First in ClinVar: May 21, 2022 Last updated: Dec 02, 2023 |
Comment:
ACMG classification criteria: PS3 moderate, PM3 very strong, PP1
Geographic origin: Brazil
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Pathogenic
(Feb 09, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002017642.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
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Pathogenic
(Aug 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000604310.5
First in ClinVar: Jun 09, 2014 Last updated: Feb 20, 2024 |
Comment:
The MUTYH c.536A>G; p.Tyr179Cys variant (rs34612342), also known as p.Tyr165Cys NM_001048171.1, has been well described in the literature as one of the two common MUTYH … (more)
The MUTYH c.536A>G; p.Tyr179Cys variant (rs34612342), also known as p.Tyr165Cys NM_001048171.1, has been well described in the literature as one of the two common MUTYH pathogenic variants. It has been observed in homozygous or compound heterozygous form with other pathogenic MUTYH variants in patients with colorectal cancer, familial adenomatous polyposis (FAP) or attenuated FAP (Aretz 2014). This variant is also report in ClinVar (Variation ID: 5293) and is found in the general population with an overall allele frequency of 0.1538% (435/282,806 alleles) in the Genome Aggregation Database. Functional studies have shown that the p.Tyr179Cys variant results in severely decreased DNA binding and adenine DNA glycosylase activity (Al-Tassan 2002, Ali 2008, Goto 2010, Molatore 2010). Computational analyses predict that this variant is deleterious (REVEL: 0.963). Based on available information, this variant is considered to be pathogenic. References: Ali M et al. Characterization of mutant MUTYH proteins associated with familial colorectal cancer. Gastroenterology. 2008; 135(2):499-507. PMID:18534194. Al-Tassan N et al. Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors. Nat Genet. 2002; 30(2):227-32. PMID:11818965. Aretz S et al. MUTYH-associated polyposis (MAP): evidence for the origin of the common European mutations p.Tyr179Cys and p.Gly396Asp by founder events. Eur J Hum Genet. 2014; 22(7):923-9. PMID:23361220. Goto M et al. Adenine DNA glycosylase activity of 14 human MutY homolog (MUTYH) variant proteins found in patients with colorectal polyposis and cancer. Hum Mutat. 2010; 31(11):E1861-74. PMID:20848659. Molatore S et al. MUTYH mutations associated with familial adenomatous polyposis: functional characterization by a mammalian cell-based assay. Hum Mutat. 2010; 31(2):159-66. PMID:19953527. (less)
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Pathogenic
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000166454.13
First in ClinVar: Jun 15, 2014 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 179 of the MUTYH protein … (more)
This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 179 of the MUTYH protein (p.Tyr179Cys). This variant is present in population databases (rs34612342, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant is a known common cause of MUTYH-associated polyposis (PMID: 23035301). This variant has been reported to co-segregate with disease in individuals affected with colorectal cancer and polyposis (with polyp numbers ranging from 10 to >100) (PMID: 12606733, 16557584, 17489848, 19793053, 21063410, 24444654). MUTYH-related conditions are inherited in an autosomal recessive fashion. However, there is evidence that monoallelic pathogenic MUTYH variants including this particular variant are associated with increased risk of colon cancer (PMID: 16492921, 19394335, 21171015, 24444654). This variant is also known as c.494A>G (p.Tyr165Cys). ClinVar contains an entry for this variant (Variation ID: 5293). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects MUTYH function (PMID: 11818965, 18534194, 19953527, 20848659). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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MUTYH-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000806361.3
First in ClinVar: Sep 13, 2018 Last updated: Mar 16, 2024 |
Comment:
The MUTYH c.536A>G variant is predicted to result in the amino acid substitution p.Tyr179Cys. This variant, also described as p.Tyr165Cys in the literature (Poulsen and … (more)
The MUTYH c.536A>G variant is predicted to result in the amino acid substitution p.Tyr179Cys. This variant, also described as p.Tyr165Cys in the literature (Poulsen and Bisgaard. 2008. PubMed ID: 19506731), is among the most common contributors to autosomal recessive MUTYH-associated polyposis (http://www.ncbi.nlm.nih.gov/books/NBK107219/) and has been shown to co-segregate with disease in multiple patients with colorectal cancer, familial adenomatous polyposis (FAP), and attenuated FAP (Sieber et al. 2003. PubMed ID: 12606733; Aretz et al. 2006. PubMed ID: 16557584; Theodoratou et al. 2010. PubMed ID: 21063410). This variant has also been observed in individuals with breast cancers with and without a family history of cancers (Wasielewski et al. 2010. PubMed ID: 20191381; Rennert et al. 2012. PubMed ID: 21952991). Several studies have shown that the p.Tyr179Cys variant disrupts MUTYH protein function (Ali et al. 2008. PubMed ID: 18534194; Molatore et al. 2010. PubMed ID: 19953527). In ClinVar, it is documented as a likely pathogenic/pathogenic variant (https://www.ncbi.nlm.nih.gov/clinvar/variation/5293/). Based on these data, we interpret this variant as pathogenic. (less)
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Pathogenic
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001248085.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Comment:
MUTYH: PS3, PS4, PP1:Moderate, PP3
Number of individuals with the variant: 19
|
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Pathogenic
(Nov 05, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
(Autosomal recessive inheritance)
Affected status: no
Allele origin:
germline
|
Molecular Genetics, Royal Melbourne Hospital
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004812763.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
This sequence change in MUTYH is predicted to replace tyrosine with cysteine at codon 151, p.(Tyr151Cys). This variant has been reported as Y179C and Y165C … (more)
This sequence change in MUTYH is predicted to replace tyrosine with cysteine at codon 151, p.(Tyr151Cys). This variant has been reported as Y179C and Y165C in literature. The tyrosine residue is highly conserved (100 vertebrates, UCSC), and is located in the nudix hydrolase domain. There is a large physicochemical difference between tyrosine and cysteine. The highest population minor allele frequency in the population database gnomAD v2.1 is 0.23% (323/129,154 alleles) in the European non-Finnish population. This variant is one of the common European founder variants and has been reported in multiple affected individuals with MUTYH-associated polyposis (PMID: 23361220; 11818965; 37469678; 35218514). The reported individuals were either homozygous or compound heterozygous for the variant. The variant has been reported to segregate in multiple affected individuals with MUTYH-associated polyposis and colorectal cancer from unrelated families (PMID: 23361220; 11818965). An in vitro functional assay showed decreased DNA glycosylase activity in the mutant vector indicating that this variant impacts protein function (PMID: 20848659). Computational evidence predicts a deleterious effect for the missense substitution (REVEL = 0.963). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PM3_VeryStrong; PP1_Strong; PP3_Moderate; PS3_Supporting (less)
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Pathogenic
(Oct 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000245637.3
First in ClinVar: Sep 14, 2015 Last updated: Apr 20, 2024 |
Comment:
The p.Tyr179Cys variant in MUTYH is a well-established pathogenic variant for MUTYH-associated polyposis, segregating with disease in multiple affected individuals (Al-Tassan 2002 PMID: 11818965, Nielsen … (more)
The p.Tyr179Cys variant in MUTYH is a well-established pathogenic variant for MUTYH-associated polyposis, segregating with disease in multiple affected individuals (Al-Tassan 2002 PMID: 11818965, Nielsen 2009 PMID: 19032956, Vogt 2009 PMID: 19732775). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID 5293) and been identified in 0.2% (323/129154) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs34612342). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Functional studies indicate this variant affects MUTYH enzyme activity (Al-Tassan 2002 PMID: 11818965, Parker 2005 PMID: 15987719, Kundu 2009 PMID: 19836313, Molatore 2009 PMID: 19953527, Grasso 2014 PMID: 24569162). In summary, this variant meets criteria to be classified as pathogenic for MUTYH-associated polyposis in an autosomal recessive manner based upon presence in multiple affected individuals, segregation and functional studies. The ACMG/AMP Criteria applied: PM3_VeryStrong, PP1_Strong, PS3_Moderate. (less)
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Pathogenic
(May 26, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000678191.1
First in ClinVar: Jan 06, 2018 Last updated: Jan 06, 2018 |
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Pathogenic
(Nov 01, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
Affected status: yes
Allele origin:
germline
|
Center for Human Genetics, Inc, Center for Human Genetics, Inc
Accession: SCV000781798.1
First in ClinVar: Jul 07, 2018 Last updated: Jul 07, 2018 |
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Pathogenic
(Sep 26, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000111384.5
First in ClinVar: Jan 22, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 10
Sex: mixed
|
|
Likely pathogenic
(Mar 26, 2019)
|
criteria provided, single submitter
Method: research
|
Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
unknown
|
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: AGHI_WGS
Accession: SCV000993434.1 First in ClinVar: Sep 22, 2019 Last updated: Sep 22, 2019 |
Number of individuals with the variant: 1
|
|
Pathogenic
(Jan 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: yes
Allele origin:
germline
|
GeneKor MSA
Accession: SCV000821743.2
First in ClinVar: Oct 10, 2018 Last updated: Apr 24, 2020 |
Comment:
This sequence change replaces tyrosine with cysteine at codon 179 of the MUTYH protein (p.Tyr179Cys). The tyrosine residue is highly conserved and there is a … (more)
This sequence change replaces tyrosine with cysteine at codon 179 of the MUTYH protein (p.Tyr179Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine (Grantham Score 194).This variant, also known as Y165C using an alternative reference sequence, has been published in the literature as one of the two common MUTYH missense mutations in Western populations, and, when found in combination with another pathogenic variant, is known to cause MUTYH-associated polyposis (MAP) (PMID: 19032956). It has been reported to co-segregate with disease in individuals affected with colorectal cancer, familial adenomatous polyposis (FAP), and attenuated FAP (PMID: 24444654; 21063410 ; 19793053 ; 17489848, 31159747) Experimental studies have shown that this variant disrupts MUTYH protein function (PMID: 20848659 ; 19953527 ; 11818965 ). The mutation database ClinVar contains entries for this variant (Variation ID:5293). (less)
|
|
Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447259.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Intestinal polyposis (present)
Sex: male
|
|
Pathogenic
(Aug 20, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001450299.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 14
|
|
Pathogenic
(Jan 25, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
Affected status: yes
Allele origin:
maternal
|
Baylor Genetics
Study: CSER-TexasKidsCanSeq
Accession: SCV001523758.2 First in ClinVar: Mar 22, 2021 Last updated: Feb 13, 2022 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
|
|
Pathogenic
(Feb 02, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: yes
Allele origin:
germline
|
AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002501272.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
|
|
Pathogenic
(Mar 07, 2022)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002532295.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The MUTYH c.536A>G (p.Y179C) variant is a well-known pathogenic variant associated with autosomal recessive MUTYH-associated polyposis. This variant, also known as c.494A>G (p.Y165C), was observed … (more)
The MUTYH c.536A>G (p.Y179C) variant is a well-known pathogenic variant associated with autosomal recessive MUTYH-associated polyposis. This variant, also known as c.494A>G (p.Y165C), was observed in 323/129154 chromosomes in the Non-Finnish European population, with no homozygotes, in the large and broad cohorts of the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). It has been reported as homozygous or compound heterozygous with other pathogenic MUTYH variants in multiple individuals with colorectal cancer and polyposis (PMID: 19732775, 19032956, 23035301). In addition, this variant has been reported to co-segregate with disease in several families (PMID: 118118965, 12606733, 16557584, 17489848, 19793053). Functional studies have shown that this variant alters MUTYH protein function (PMID: 19836313, 20418187). Monoallelic carriers of this variant have shown a slightly increased risk for colorectal cancer (PMID: 19394335, 21063410, 24444654). The variant has been reported in ClinVar (Variation ID: 5293). Based on the current evidence available, this variant is interpreted as pathogenic. (less)
|
|
|
Pathogenic
(Jul 29, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002581711.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PM3_VSTR, PS3, PS4_MOD, PM2_SUP, PP1, PP3
|
Number of individuals with the variant: 16
Sex: female
|
|
Pathogenic
(Jul 02, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
MYH-associated polyposis
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV000837775.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
|
|
Pathogenic
(Apr 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002761566.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
Comment:
The heterozygous variant c.536A>G detected in exon 7 of the MUTYH gene is a missense change resulting in an amino acid substitution from a Tyrosine … (more)
The heterozygous variant c.536A>G detected in exon 7 of the MUTYH gene is a missense change resulting in an amino acid substitution from a Tyrosine to a Cysteine at codon 179, p.(Tyr179Cys). This variant has been reported multiple times in both LOVD and ClinVar databases as pathogenic. This variant is one of the common MUTYH pathogenic founder mutations in European populations, which has been reported to co-segregate with colorectal cancer and MUTYH-associated polyposis (MAP) (Aretz et al, Eur J Hum Genet (2014) 22(7):923-9 and Theodoratou et al, British Journal of Cancer (2010) 103(12):1875-84). In populations of European origin, the missense variants p.(Tyr179Cys) and p.(Gly396Asp) account for up to 80% of MUTYH variants identified in MAP patients (Sieber et al, N Engl J Med (2003) 348(9):791-9; Kanter-Smoler et al, Clin Gastroenterol Hepatol (2006) 4(4):499-506 and Aretz et al, Eur J Hum Genet (2014) 22(7):923-9). In healthy controls from different populations, the allele frequencies for this variant range from 0.04 to 0.4% (Aretz et al, Eur J Hum Genet (2014) 22(7):923-9). Functional studies have shown that this missense change disrupts MUTYH protein function (Parker et al, Carcinogenesis, (2005) 26(11):2010-18; Mohsin et al, Gastroentorology (2008) 135(2):499-507 and Ruggieri et al, Oncogene (2013) 32(38):4500-8). Based on current knowledge, this is a pathogenic (Class 5) variant. This patient is a heterozygous carrier of a recessive condition. (less)
|
|
Pathogenic
(Mar 15, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
Gastric cancer
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000611286.2
First in ClinVar: Nov 11, 2017 Last updated: Dec 31, 2022 |
|
|
Pathogenic
(Feb 26, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000149675.17
First in ClinVar: May 17, 2014 Last updated: Mar 04, 2023 |
Comment:
One of two common MUTYH pathogenic variants which together account for up to 80% of pathogenic MUTYH variants (Cleary 2009); Observed in the homozygous and … (more)
One of two common MUTYH pathogenic variants which together account for up to 80% of pathogenic MUTYH variants (Cleary 2009); Observed in the homozygous and compound heterozygous state in multiple individuals with MUTYH-Associated Polyposis (Nielsen 2009, de Leon 2017, DeRycke 2017, Furlan 2017); Published functional studies demonstrate a damaging effect: reduced glycosylase and DNA binding activity (Ali 2008, Goto 2010, Komine 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as p.Tyr165Cys; This variant is associated with the following publications: (PMID: 21178863, 19998059, 19032956, 20418187, 19836313, 20571908, 19300419, 22744763, 27153395, 25980754, 27705013, 28944238, 28141798, 20848659, 30256826, 30609409, 29506128, 22703879, 21063410, 22926731, 23361220, 18534194, 19732775, 19953527, 24733792, 23108399, 24728327, 25931827, 24569162, 11818965, 12606733, 17489848, 19793053, 16557584, 24444654, 16492921, 19394335, 21171015, 17039270, 27498913, 25820570, 27829682, 27631816, 27978560, 26446593, 27797849, 26681312, 26202870, 28709830, 28873162, 28503720, 27696107, 27799157, 27783336, 28591191, 29557500, 26517685, 26556299, 30953464, 30067863, 30564557, 30582135, 30604180, 30833417, 31159747, 30676620, 30877237, 31921681, 30306255, 32088803, 30291343, 31447099, 31263571, 32283892, 31980526, 23035301, 34026625, 34426522, 34259353, 31589614, 33193653, 33384714, 32338768, 33258288, 32615015, 32830346, 33504652, 33332384, 30613976, 33442023) (less)
|
|
Pathogenic
(Feb 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697700.2
First in ClinVar: Mar 17, 2018 Last updated: Mar 26, 2023 |
Comment:
Variant summary: MUTYH c.536A>G (p.Tyr179Cys) results in a non-conservative amino acid change located in the HhH-GPD domain (IPR003265) of the encoded protein sequence. Five of … (more)
Variant summary: MUTYH c.536A>G (p.Tyr179Cys) results in a non-conservative amino acid change located in the HhH-GPD domain (IPR003265) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0015 in 251454 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in MUTYH causing MUTYH-Associated Polyposis (0.0015 vs 0.0046), allowing no conclusion about variant significance. c.536A>G has been reported in the literature in many individuals affected with MUTYH-Associated Polyposis (e.g., Kanter-Smoler, Nielsen_2005). These data indicate that the variant is very likely to be associated with disease. Several publications report experimental evidence evaluating an impact on protein function, finding that the variant causes loss of protein function, resulting in defective DNA-binding and glycosylase activities (e.g., Komine_2015, Ali_2008). 38 ClinVar submitters (evaluation after 2014) have cited the variant, and all laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
Pathogenic
(Mar 18, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000691950.3
First in ClinVar: Feb 19, 2018 Last updated: Jun 03, 2023 |
Comment:
PP1, PP3, PP5, PM3, PVS1
|
|
Pathogenic
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002011058.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
|
|
Pathogenic
(Oct 31, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004198793.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
Pathogenic
(Mar 08, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000601651.4
First in ClinVar: Mar 08, 2017 Last updated: Jan 06, 2024 |
Comment:
In the published literature, this variant has been reported in multiple individuals affected with MUTYH-associated polyposis (MAP), and is reported to be one of two … (more)
In the published literature, this variant has been reported in multiple individuals affected with MUTYH-associated polyposis (MAP), and is reported to be one of two pathogenic variants associated with MAP in individuals of European ancestry (PMIDs: 12606733 (2003), 17489848 (2007), 19793053 (2009), 23361220 (2014)). In addition, this variant has been reported as having a deleterious effect on MUTYH protein function (PMIDs: 24569162 (2014), 20418187 (2010), 19836313 (2009), 19032956 (2009)). Based on the available information, this variant is classified as pathogenic. (less)
|
|
Pathogenic
(Feb 06, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002552516.5
First in ClinVar: Jul 23, 2022 Last updated: Feb 14, 2024 |
|
|
Pathogenic
(Feb 20, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000537631.5
First in ClinVar: Mar 24, 2017 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces tyrosine with cysteine at codon 179 of the MUTYH protein. This variant is also known as p.Tyr165Cys (c.494A>G) based on an … (more)
This missense variant replaces tyrosine with cysteine at codon 179 of the MUTYH protein. This variant is also known as p.Tyr165Cys (c.494A>G) based on an alternate transcript, NM_001048171. Computational prediction tool suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that the mutant protein is defective in DNA binding and repair, and glycosylase activity (PMID: 18534194, 19953527). This variant is a well-established pathogenic variant known to cause adenomatous polyposis and colorectal cancer in homozygous and compound heterozygous individuals (PMID: 11818965, 12606733, 16338133, 16492921, 16557584, 17489848, 18534194, 19032956, 19394335, 19793053, 20418187, 21063410, 21171015, 22266422, 23361220, 24444654, 27829682). This variant is one of two most common pathogenic MUTYH variants, which together account for up to 80% of MUTYH-associated disease observed in Caucasian individuals (PMID: 29147111). This variant has been identified in 435/282806 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
|
|
Pathogenic
(Feb 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 2
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004839638.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
The c.536A>G (p.Tyr179Cys) variant in the MUTYH gene is located on the exon 7 of the MUTYH gene and is predicted to replace tyrosine with … (more)
The c.536A>G (p.Tyr179Cys) variant in the MUTYH gene is located on the exon 7 of the MUTYH gene and is predicted to replace tyrosine with cysteine at codon 179 of the MUTYH protein. This variant has been observed in homozygous or compound heterozygous state in multiple individuals with MUTYH-associated polyposis and colorectal cancer (PMID: 11818965, 12606733, 16338133, 16492921, 16557584, 17489848, 18534194, 19032956, 19394335, 19793053, 20418187, 21063410, 21171015, 22266422, 23361220, 24444654, 27829682). This variant has been reported to co-segregate with disease in multiple individuals (PMID: 12606733, 16557584, 17489848, 19793053, 21063410, 24444654). Functional studies have shown that the mutant protein is defective in DNA binding and repair, and glycosylase activity (PMID:11818965, 18534194, 19953527, 20848659). This missense change has been identified in 435/282806 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Computational prediction suggests that this variant may have deleterious impact on protein structure and function (REVEL score %3D 0.963). Based on these evidence, the c.536A>G(p.Tyr179Cys) variant in the MUTYH gene is classified as pathogenic. This finding is consistent with an asymptomatic carrier status of familial adenomatous polyposis in this individual, provided there are no deleterious alterations of the remaining MUTYH allele. (less)
Number of individuals with the variant: 360
|
|
Pathogenic
(Feb 16, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000185514.10
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The c.536A>G (p.Y179C) alteration is located in coding exon 7 of the MUTYH gene. This alteration results from a A to G substitution at nucleotide … (more)
The c.536A>G (p.Y179C) alteration is located in coding exon 7 of the MUTYH gene. This alteration results from a A to G substitution at nucleotide position 536, causing the tyrosine (Y) at amino acid position 179 to be replaced by a cysteine (C). Based on data from gnomAD, the G allele has an overall frequency of 0.154% (435/282806) total alleles studied. The highest observed frequency was 0.25% (323/129154) of European (non-Finnish) alleles. This alteration represents a founder mutation in multiple populations and accounts for a significant proportion of pathogenic MUTYH mutations reported to date (Nielsen, 2009; Aretz, 2014). A 2-fold increased risk of colorectal cancer (CRC) risk for carriers of a single (mono-allelic) MUTYH mutation has been reported as similar to the CRC risk of those with an affected first degree relative (Jones, 2009; Butterworth, 2006). A large scale meta-analysis to refine CRC risk estimates associated with MUTYH variants, including more than 20000 cases and 15000 controls, demonstrated an approximately 1.5 fold increase in CRC risk for carriers of the p.Y179C mutation (Theodoratou, 2010). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. (less)
|
|
Pathogenic
(Dec 01, 2007)
|
no assertion criteria provided
Method: literature only
|
FAMILIAL ADENOMATOUS POLYPOSIS 2
Affected status: not provided
Allele origin:
unknown
|
OMIM
Accession: SCV000025794.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In a Welsh family in which 3 sibs had familial adenomatous polyposis-2 (FAP2; 608456), Al-Tassan et al. (2002) could find no clear germline pathogenic change … (more)
In a Welsh family in which 3 sibs had familial adenomatous polyposis-2 (FAP2; 608456), Al-Tassan et al. (2002) could find no clear germline pathogenic change in the APC gene. However, they showed that 11 tumors from the 3 affected sibs contained 18 somatic inactivating mutations of APC and that 15 of these mutations were G:C-T:A transversions--a significantly greater proportion than is found in sporadic tumors or in tumors associated with familial adenomatous polyposis. Analysis of the mutY gene showed that the affected sibs were compound heterozygous for 2 missense variants, tyr165 to cys (Y165C) and gly382 to asp (G382D; 604933.0002). Thus, defective base excision repair was implicated by these findings in predisposition to tumors in humans. Sieber et al. (2003) found the germline Y165C mutation in homozygous or compound heterozygous state in 5 of 12 patients from the UK with multiple adenomas. Barnetson et al. (2007) reported a patient with endometrial adenocarcinoma (see 608089) and sebaceous carcinoma of the face who was compound heterozygous for the Y165C and G382D mutations. Colonic adenomas were not reported, but a paternal aunt reportedly had colorectal cancer in her thirties. Barnetson et al. (2007) noted that the phenotype associated with biallelic MUTYH mutations may include extracolonic manifestations, including endometrial cancer and sebaceous carcinoma, as seen in other inherited colorectal cancer syndromes. (less)
|
|
Pathogenic
(Dec 01, 2007)
|
no assertion criteria provided
Method: literature only
|
ENDOMETRIAL CANCER
Affected status: not provided
Allele origin:
unknown
|
OMIM
Accession: SCV000025795.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In a Welsh family in which 3 sibs had familial adenomatous polyposis-2 (FAP2; 608456), Al-Tassan et al. (2002) could find no clear germline pathogenic change … (more)
In a Welsh family in which 3 sibs had familial adenomatous polyposis-2 (FAP2; 608456), Al-Tassan et al. (2002) could find no clear germline pathogenic change in the APC gene. However, they showed that 11 tumors from the 3 affected sibs contained 18 somatic inactivating mutations of APC and that 15 of these mutations were G:C-T:A transversions--a significantly greater proportion than is found in sporadic tumors or in tumors associated with familial adenomatous polyposis. Analysis of the mutY gene showed that the affected sibs were compound heterozygous for 2 missense variants, tyr165 to cys (Y165C) and gly382 to asp (G382D; 604933.0002). Thus, defective base excision repair was implicated by these findings in predisposition to tumors in humans. Sieber et al. (2003) found the germline Y165C mutation in homozygous or compound heterozygous state in 5 of 12 patients from the UK with multiple adenomas. Barnetson et al. (2007) reported a patient with endometrial adenocarcinoma (see 608089) and sebaceous carcinoma of the face who was compound heterozygous for the Y165C and G382D mutations. Colonic adenomas were not reported, but a paternal aunt reportedly had colorectal cancer in her thirties. Barnetson et al. (2007) noted that the phenotype associated with biallelic MUTYH mutations may include extracolonic manifestations, including endometrial cancer and sebaceous carcinoma, as seen in other inherited colorectal cancer syndromes. (less)
|
|
pathogenic
(Jul 13, 2012)
|
no assertion criteria provided
Method: research
|
MYH-associated polyposis
Affected status: no
Allele origin:
germline
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043377.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Pathogenic.
Number of individuals with the variant: 2
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Carcinoma of colon
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000592686.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The MUTYH p.Tyr179Cys variant was identified in 878 of 42,504 proband chromosomes (frequency: 0.03) from individuals or families with MAP or colorectal cancer (CRC). Of … (more)
The MUTYH p.Tyr179Cys variant was identified in 878 of 42,504 proband chromosomes (frequency: 0.03) from individuals or families with MAP or colorectal cancer (CRC). Of these 292 were heterozygous carriers, 99 were homozygous and 487 were compound heterozygotes. The variant was present in 156 of 31,262 control chromosomes (frequency: 0.005) from healthy individuals (Al-Tassan 2002, Nielsen 2009, Nascimbeni 2010, Theodoratou 2010, Vogt 2009, Sieber 2003). The variant was also identified in dbSNP (ID: rs34612342) as With Pathogenic allele, ClinVar (classified as pathogenic by GeneDx, Invitae, Ambry Genetics, Color Genomics, Pathway Genomics and more), Clinvitae (classified as pathogenic by ClinVar and Invitae), Cosmic (pathogenic), and in Insight Colon Cancer Gene Variant Database (535x pathogenic). The variant was not identified in MutDB, or UMD-LSDB databases. The variant was identified in control databases in 412 of 277178 chromosomes at a frequency of 0.001486 (Genome Aggregation Consortium Feb 27, 2017). The p.Tyr179 residue is conserved in mammals but not in more distantly related organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In a meta-analysis study (Theodoratou 2010), to assess and refine CRC risk estimates associated with bi-allelic and mono-allelic MUTYH variants, MUTYH bi-allelic carriers demonstrated a 28-fold increase in CRC risk. Significant bi-allelic effects were also observed for G396D and Y179C/G396D compound heterozygotes and a marginal mono-allelic effect for variant Y179C. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
|
|
Pathogenic
(Jul 21, 2023)
|
no assertion criteria provided
Method: research
|
Familial adenomatous polyposis 2
Affected status: yes
Allele origin:
germline
|
deCODE genetics, Amgen
Accession: SCV004022111.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
Comment:
The variant NM_001048174.2:c.452A>G (chr1:45332803) in MUTYH was detected in 236 heterozygotes and 2 homozygotes out of 58K WGS Icelanders (MAF= 0,2%). Following imputation in a … (more)
The variant NM_001048174.2:c.452A>G (chr1:45332803) in MUTYH was detected in 236 heterozygotes and 2 homozygotes out of 58K WGS Icelanders (MAF= 0,2%). Following imputation in a set of 166K Icelanders (658 heterozygotes and 2 homozygotes) we observed an association with colorectal cancer under a recessive model using 4991 cases and 314812 controls (OR= 60.78, P= 3.57e-03). This variant has been reported in ClinVar previously as pathogenic/likely pathogenic. Based on ACMG criteria (PS3, PS4, PM2, PP5) this variant classifies as pathogenic. (less)
Number of individuals with the variant: 2
Ethnicity/Population group: Icelandic
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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: SCV000189958.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
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Pathogenic
(Oct 13, 2014)
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no assertion criteria provided
Method: clinical testing
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MYH-associated polyposis
(Autosomal recessive inheritance)
Affected status: no
Allele origin:
germline
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Knight Diagnostic Laboratories, Oregon Health and Sciences University
Accession: SCV000223938.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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Pathogenic
(Dec 08, 2017)
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no assertion criteria provided
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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True Health Diagnostics
Accession: SCV000788070.1
First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: yes
Allele origin:
germline
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Genomics England Pilot Project, Genomics England
Accession: SCV001760036.1
First in ClinVar: Jul 31, 2021 Last updated: Jul 31, 2021 |
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Likely pathogenic
(Aug 07, 2021)
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no assertion criteria provided
Method: clinical testing
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Gastric cancer
Affected status: yes
Allele origin:
germline
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Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences
Accession: SCV001774805.1
First in ClinVar: Aug 14, 2021 Last updated: Aug 14, 2021 |
Comment:
Invasive Ductal Carcinoma Estrogen Receptor: Negative Progesterone Receptor: Negative HER2 Receptor: Positive
Age: 30-39 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: SCV001797531.1 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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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001807834.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 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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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001739761.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 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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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001921303.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 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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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927195.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 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: SCV001952423.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 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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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001971114.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
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not provided
(-)
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no classification provided
Method: phenotyping only
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
unknown
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GenomeConnect, ClinGen
Accession: SCV002074923.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
Comment:
Variant interpreted as Pathogenic and reported on 07-22-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpreted as Pathogenic and reported on 07-22-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Abnormality of the nose (present) , Myopia (present) , Anxiety (present) , Depression (present) , Abnormal pattern of respiration (present) , Abnormal esophagus morphology (present) … (more)
Abnormality of the nose (present) , Myopia (present) , Anxiety (present) , Depression (present) , Abnormal pattern of respiration (present) , Abnormal esophagus morphology (present) , Abnormality of the bladder (present) , Abnormality of the female genitalia (present) , Breast carcinoma (present) , Thyroid tumor (present) (less)
Indication for testing: Family Testing
Age: 40-49 years
Sex: female
Testing laboratory: Invitae
Date variant was reported to submitter: 2020-07-22
Testing laboratory interpretation: Pathogenic
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not provided
(-)
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no classification provided
Method: literature only
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000057869.6
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
Comment:
Common pathogenic variants carried by approximately 1%-2% of the general population that account for =90% of all MUTYH pathogenic variants in northern European populations; =70% … (more)
Common pathogenic variants carried by approximately 1%-2% of the general population that account for =90% of all MUTYH pathogenic variants in northern European populations; =70% of persons with MUTYH-Associated Polyposis (MAP) harbor at least 1 of these variants, 536A>G or 1187G>A (less)
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000085805.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
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Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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not provided
(-)
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no classification provided
Method: phenotyping only
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
unknown
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GenomeConnect - Invitae Patient Insights Network
Accession: SCV001749490.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Comment:
Variant reported in multiple Invitae PIN participants. Variant interpreted as Pathogenic and reported most recently on 3/24/2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are … (more)
Variant reported in multiple Invitae PIN participants. Variant interpreted as Pathogenic and reported most recently on 3/24/2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Family history (present)
Indication for testing: Diagnostic
Age: 60-69 years
Sex: female
Testing laboratory: Invitae
Date variant was reported to submitter: 2018-10-04
Testing laboratory interpretation: Pathogenic
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Family history of cancer (present)
Indication for testing: Presymptomatic|Family Testing|family history
Age: 30-39 years
Sex: female
Testing laboratory: Invitae
Date variant was reported to submitter: 2020-03-24
Testing laboratory interpretation: Pathogenic
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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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The genetic structure of the Turkish population reveals high levels of variation and admixture. | Kars ME | Proceedings of the National Academy of Sciences of the United States of America | 2021 | PMID: 34426522 |
Exome sequencing of familial adenomatous polyposis-like individuals identifies both known and novel causative genes. | Xavier A | Clinical genetics | 2021 | PMID: 34259353 |
Exome sequencing in BRCA1-2 candidate familias: the contribution of other cancer susceptibility genes. | Doddato G | Frontiers in oncology | 2021 | PMID: 34026625 |
Whole-exome sequencing reveals germline-mutated small cell lung cancer subtype with favorable response to DNA repair-targeted therapies. | Tlemsani C | Science translational medicine | 2021 | PMID: 33504652 |
Prevalence of pathogenic germline variants in patients with metastatic renal cell carcinoma. | Santos M | Genetics in medicine : official journal of the American College of Medical Genetics | 2021 | PMID: 33442023 |
Pathogenic germline variants in patients with features of hereditary renal cell carcinoma: Evidence for further locus heterogeneity. | Smith PS | Genes, chromosomes & cancer | 2021 | PMID: 32830346 |
MUTYH Polyposis. | Adam MP | - | 2021 | PMID: 23035301 |
Case Report: The Role of Molecular Analysis of the MUTYH Gene in Asymptomatic Individuals. | Fabišíková K | Frontiers in genetics | 2020 | PMID: 33384714 |
Nationwide germline whole genome sequencing of 198 consecutive pediatric cancer patients reveals a high incidence of cancer prone syndromes. | Byrjalsen A | PLoS genetics | 2020 | PMID: 33332384 |
Diagnostic power and clinical impact of exome sequencing in a cohort of 500 patients with rare diseases. | Quaio CRDC | American journal of medical genetics. Part C, Seminars in medical genetics | 2020 | PMID: 33258288 |
New Pathogenic Germline Variants in Very Early Onset and Familial Colorectal Cancer Patients. | Djursby M | Frontiers in genetics | 2020 | PMID: 33193653 |
Digenic inheritance of MSH6 and MUTYH variants in familial colorectal cancer. | Schubert SA | Genes, chromosomes & cancer | 2020 | PMID: 32615015 |
Rare germline genetic variants and risk of aggressive prostate cancer. | Nguyen-Dumont T | International journal of cancer | 2020 | PMID: 32338768 |
Spectrum of germline cancer susceptibility gene mutations in Turkish colorectal cancer patients: a single center study. | Erdem HB | Turkish journal of medical sciences | 2020 | PMID: 32283892 |
Increased prevalence of Barrett's esophagus in patients with MUTYH-associated polyposis (MAP). | Daans CG | Familial cancer | 2020 | PMID: 32088803 |
Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging. | Hou YC | Proceedings of the National Academy of Sciences of the United States of America | 2020 | PMID: 31980526 |
Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach. | Oliver J | Frontiers in oncology | 2019 | PMID: 31921681 |
Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. | Capalbo A | PLoS genetics | 2019 | PMID: 31589614 |
Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network. | eMERGE Consortium. Electronic address: agibbs@bcm.edu | American journal of human genetics | 2019 | PMID: 31447099 |
High frequency of pathogenic germline variants within homologous recombination repair in patients with advanced cancer. | Bertelsen B | NPJ genomic medicine | 2019 | PMID: 31263571 |
Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations. | Tsaousis GN | BMC cancer | 2019 | PMID: 31159747 |
Intussusception reveals MUTYH-associated polyposis syndrome and colorectal cancer: a case report. | de Mesquita GHA | BMC cancer | 2019 | PMID: 30953464 |
Clinical characteristics of patients with colorectal cancer with double somatic mismatch repair mutations compared with Lynch syndrome. | Pearlman R | Journal of medical genetics | 2019 | PMID: 30877237 |
Base excision repair deficiency signatures implicate germline and somatic MUTYH aberrations in pancreatic ductal adenocarcinoma and breast cancer oncogenesis. | Thibodeau ML | Cold Spring Harbor molecular case studies | 2019 | PMID: 30833417 |
Association of Inherited Pathogenic Variants in Checkpoint Kinase 2 (CHEK2) With Susceptibility to Testicular Germ Cell Tumors. | AlDubayan SH | JAMA oncology | 2019 | PMID: 30676620 |
Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy. | Rizzolo P | International journal of cancer | 2019 | PMID: 30613976 |
Interpretation of Genomic Sequencing Results in Healthy and Ill Newborns: Results from the BabySeq Project. | Ceyhan-Birsoy O | American journal of human genetics | 2019 | PMID: 30609409 |
Multi-gene panel testing confirms phenotypic variability in MUTYH-Associated Polyposis. | Sutcliffe EG | Familial cancer | 2019 | PMID: 30604180 |
Monoallelic MUTYH carrier status is not associated with increased breast cancer risk in a multigene panel cohort. | Fulk K | Familial cancer | 2019 | PMID: 30582135 |
1 in 38 individuals at risk of a dominant medically actionable disease. | Haer-Wigman L | European journal of human genetics : EJHG | 2019 | PMID: 30291343 |
Contribution of MUTYH Variants to Male Breast Cancer Risk: Results From a Multicenter Study in Italy. | Rizzolo P | Frontiers in oncology | 2018 | PMID: 30564557 |
Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings. | Bonache S | Journal of cancer research and clinical oncology | 2018 | PMID: 30306255 |
Novel genetic mutations detected by multigene panel are associated with hereditary colorectal cancer predisposition. | Martin-Morales L | PloS one | 2018 | PMID: 30256826 |
Prospective study of germline genetic testing in incident cases of pancreatic adenocarcinoma. | Brand R | Cancer | 2018 | PMID: 30067863 |
Incidental and clinically actionable genetic variants in 1005 whole exomes and genomes from Qatar. | Jain A | Molecular genetics and genomics : MGG | 2018 | PMID: 29557500 |
Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms. | Lowery MA | Journal of the National Cancer Institute | 2018 | PMID: 29506128 |
Hereditary Colorectal Tumors: A Literature Review on MUTYH-Associated Polyposis. | Kantor M | Gastroenterology research and practice | 2017 | PMID: 29147111 |
Targeted sequencing of 36 known or putative colorectal cancer susceptibility genes. | DeRycke MS | Molecular genetics & genomic medicine | 2017 | PMID: 28944238 |
Pathologic findings in breast, fallopian tube, and ovary specimens in non-BRCA hereditary breast and/or ovarian cancer syndromes: a study of 18 patients with deleterious germline mutations in RAD51C, BARD1, BRIP1, PALB2, MUTYH, or CHEK2. | Schoolmeester JK | Human pathology | 2017 | PMID: 28709830 |
Contribution of germline mutations in cancer predisposition genes to tumor etiology in young women diagnosed with invasive breast cancer. | Rummel SK | Breast cancer research and treatment | 2017 | PMID: 28503720 |
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 |
Disseminated pilomyxoid astrocytoma in infancy with novel MUTYH mutation. | Aghajan Y | BMJ case reports | 2016 | PMID: 27797849 |
Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. | Maxwell KN | American journal of human genetics | 2016 | PMID: 27153395 |
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. | Susswein LR | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26681312 |
Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA. | Schrader KA | JAMA oncology | 2016 | PMID: 26556299 |
Germ-line variants identified by next generation sequencing in a panel of estrogen and cancer associated genes correlate with poor clinical outcome in Lynch syndrome patients. | Jóri B | Oncotarget | 2015 | PMID: 26517685 |
Risk of colorectal cancer for people with a mutation in both a MUTYH and a DNA mismatch repair gene. | Win AK | Familial cancer | 2015 | PMID: 26202870 |
Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome. | Yurgelun MB | Gastroenterology | 2015 | PMID: 25980754 |
Functional Complementation Assay for 47 MUTYH Variants in a MutY-Disrupted Escherichia coli Strain. | Komine K | Human mutation | 2015 | PMID: 25820570 |
Clinical evaluation of a multiple-gene sequencing panel for hereditary cancer risk assessment. | Kurian AW | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2014 | PMID: 24733792 |
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. | Bodian DL | PloS one | 2014 | PMID: 24728327 |
Genetic instability in lymphoblastoid cell lines expressing biallelic and monoallelic variants in the human MUTYH gene. | Grasso F | Human molecular genetics | 2014 | PMID: 24569162 |
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 colorectal cancer and adenomatous polyposis. | Yamaguchi S | Surgery today | 2014 | PMID: 23605219 |
MUTYH-associated polyposis (MAP): evidence for the origin of the common European mutations p.Tyr179Cys and p.Gly396Asp by founder events. | Aretz S | European journal of human genetics : EJHG | 2014 | PMID: 23361220 |
Loss of MUTYH function in human cells leads to accumulation of oxidative damage and genetic instability. | Ruggieri V | Oncogene | 2013 | PMID: 23108399 |
Cancer-associated variants and a common polymorphism of MUTYH exhibit reduced repair of oxidative DNA damage using a GFP-based assay in mammalian cells. | Raetz AG | Carcinogenesis | 2012 | PMID: 22926731 |
High prevalence of the c.1227_1228dup (p.Glu410GlyfsX43) mutation in Tunisian families affected with MUTYH-associated-polyposis. | Abdelmaksoud-Dammak R | Familial cancer | 2012 | PMID: 22744763 |
Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. | Johnston JJ | American journal of human genetics | 2012 | PMID: 22703879 |
The first mutations in the MYH gene reported in Moroccan colon cancer patients. | Laarabi FZ | Gene | 2012 | PMID: 22266422 |
Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer. | Win AK | International journal of cancer | 2011 | PMID: 21171015 |
MUTYH Tyr165Cys, OGG1 Ser326Cys and XPD Lys751Gln polymorphisms and head neck cancer susceptibility: a case control study. | Sliwinski T | Molecular biology reports | 2011 | PMID: 20571908 |
Rectum-sparing surgery may be appropriate for biallelic MutYH-associated polyposis. | Nascimbeni R | Diseases of the colon and rectum | 2010 | PMID: 21178863 |
A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants. | Theodoratou E | British journal of cancer | 2010 | PMID: 21063410 |
Adenine DNA glycosylase activity of 14 human MutY homolog (MUTYH) variant proteins found in patients with colorectal polyposis and cancer. | Goto M | Human mutation | 2010 | PMID: 20848659 |
Leiden Open Variation Database of the MUTYH gene. | Out AA | Human mutation | 2010 | PMID: 20725929 |
Functional analysis of MUTYH mutated proteins associated with familial adenomatous polyposis. | D'Agostino VG | DNA repair | 2010 | PMID: 20418187 |
Biallelic MYH germline mutations as cause of Muir-Torre syndrome. | Guillén-Ponce C | Familial cancer | 2010 | PMID: 19998059 |
MUTYH mutations associated with familial adenomatous polyposis: functional characterization by a mammalian cell-based assay. | Molatore S | Human mutation | 2010 | PMID: 19953527 |
Adenine removal activity and bacterial complementation with the human MutY homologue (MUTYH) and Y165C, G382D, P391L and Q324R variants associated with colorectal cancer. | Kundu S | DNA repair | 2009 | PMID: 19836313 |
APC or MUTYH mutations account for the majority of clinically well-characterized families with FAP and AFAP phenotype and patients with more than 30 adenomas. | Filipe B | Clinical genetics | 2009 | PMID: 19793053 |
Expanded extracolonic tumor spectrum in MUTYH-associated polyposis. | Vogt S | Gastroenterology | 2009 | PMID: 19732775 |
Increased colorectal cancer incidence in obligate carriers of heterozygous mutations in MUTYH. | Jones N | Gastroenterology | 2009 | PMID: 19394335 |
Polymorphisms of the DNA base excision repair gene MUTYH in head and neck cancer. | Sliwinski T | Experimental oncology | 2009 | PMID: 19300419 |
Germline MutY human homologue mutations and colorectal cancer: a multisite case-control study. | Cleary SP | Gastroenterology | 2009 | PMID: 19245865 |
Analysis of MUTYH genotypes and colorectal phenotypes in patients With MUTYH-associated polyposis. | Nielsen M | Gastroenterology | 2009 | PMID: 19032956 |
Characterization of mutant MUTYH proteins associated with familial colorectal cancer. | Ali M | Gastroenterology | 2008 | PMID: 18534194 |
Germline mutation prevalence in the base excision repair gene, MYH, in patients with endometrial cancer. | Barnetson RA | Clinical genetics | 2007 | PMID: 17956577 |
Germline mutations in APC and MUTYH are responsible for the majority of families with attenuated familial adenomatous polyposis. | Nielsen M | Clinical genetics | 2007 | PMID: 17489848 |
Novel findings in Swedish patients with MYH-associated polyposis: mutation detection and clinical characterization. | Kanter-Smoler G | Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | 2006 | PMID: 16616356 |
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 |
Risk of colorectal cancer in monoallelic and biallelic carriers of MYH mutations: a population-based case-family study. | Jenkins MA | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2006 | PMID: 16492921 |
Relative and absolute risk of colorectal cancer for individuals with a family history: a meta-analysis. | Butterworth AS | European journal of cancer (Oxford, England : 1990) | 2006 | PMID: 16338133 |
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 |
Cells with pathogenic biallelic mutations in the human MUTYH gene are defective in DNA damage binding and repair. | Parker AR | Carcinogenesis | 2005 | PMID: 15987719 |
Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. | Sieber OM | The New England journal of medicine | 2003 | PMID: 12606733 |
Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors. | Al-Tassan N | Nature genetics | 2002 | PMID: 11818965 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MUTYH | - | - | - | - |
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Text-mined citations for rs34612342 ...
HelpRecord last updated May 01, 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.