This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.497dup (p.Glu167fs)
Germline
Classification
Help
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.
(2)
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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.
Pathogenic
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001048174.2(MUTYH):c.497dup (p.Glu167fs)
Variation ID: 1992918 Accession: VCV001992918.3
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 1p34.1 1: 45332682-45332683 (GRCh38) [ NCBI UCSC ] 1: 45798354-45798355 (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 Feb 8, 2023 Feb 20, 2024 Mar 28, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001048174.2:c.497dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001041639.1:p.Glu167fs frameshift NM_001128425.2:c.581dup MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Glu195fs frameshift NM_001048171.2:c.497dup NP_001041636.2:p.Glu167fs frameshift NM_001048172.2:c.500dup NP_001041637.1:p.Glu168fs frameshift NM_001048173.2:c.497dup NP_001041638.1:p.Glu167fs frameshift NM_001293190.2:c.542dup NP_001280119.1:p.Glu182fs frameshift NM_001293191.2:c.530dup NP_001280120.1:p.Glu178fs frameshift NM_001293192.2:c.221dup NP_001280121.1:p.Glu75fs frameshift NM_001293195.2:c.497dup NP_001280124.1:p.Glu167fs frameshift NM_001293196.2:c.221dup NP_001280125.1:p.Glu75fs frameshift NM_001350650.2:c.152dup NP_001337579.1:p.Glu52fs frameshift NM_001350651.2:c.152dup NP_001337580.1:p.Glu52fs frameshift NM_001407069.1:c.530dup NP_001393998.1:p.Glu178Argfs frameshift NM_001407070.1:c.497dup NP_001393999.1:p.Glu167Argfs frameshift NM_001407071.1:c.500dup NP_001394000.1:p.Glu168Argfs frameshift NM_001407072.1:c.497dup NP_001394001.1:p.Glu167Argfs frameshift NM_001407073.1:c.497dup NP_001394002.1:p.Glu167Argfs frameshift NM_001407075.1:c.413dup NP_001394004.1:p.Glu139Argfs frameshift NM_001407077.1:c.530dup NP_001394006.1:p.Glu178Argfs frameshift NM_001407078.1:c.500dup NP_001394007.1:p.Glu168Argfs frameshift NM_001407079.1:c.458dup NP_001394008.1:p.Glu154Argfs frameshift NM_001407080.1:c.455dup NP_001394009.1:p.Glu153Argfs frameshift NM_001407081.1:c.497dup NP_001394010.1:p.Glu167Argfs frameshift NM_001407082.1:c.152dup NP_001394011.1:p.Glu52Argfs frameshift NM_001407083.1:c.539dup NP_001394012.1:p.Glu181Argfs frameshift NM_001407085.1:c.539dup NP_001394014.1:p.Glu181Argfs frameshift NM_001407086.1:c.500dup NP_001394015.1:p.Glu168Argfs frameshift NM_001407087.1:c.518dup NP_001394016.1:p.Glu174Argfs frameshift NM_001407088.1:c.497dup NP_001394017.1:p.Glu167Argfs frameshift NM_001407089.1:c.497dup NP_001394018.1:p.Glu167Argfs frameshift NM_001407091.1:c.221dup NP_001394020.1:p.Glu75Argfs frameshift NM_012222.3:c.572dup NP_036354.1:p.Glu192fs frameshift NR_146882.2:n.725dup non-coding transcript variant NR_146883.2:n.574dup non-coding transcript variant NR_176269.1:n.721dup NR_176270.1:n.661dup NR_176271.1:n.584dup NR_176272.1:n.648dup NR_176273.1:n.606dup NR_176274.1:n.661dup NC_000001.11:g.45332683dup NC_000001.10:g.45798355dup NG_008189.1:g.12788dup LRG_220:g.12788dup LRG_220t1:c.581dup LRG_220p1:p.Glu195Argfs - Protein change
- E168fs, E195fs, E75fs, E178fs, E182fs, E192fs, E167fs, E52fs
- Other names
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- Canonical SPDI
- NC_000001.11:45332682:A:AA
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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.
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- Links
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 | ||
|---|---|---|---|---|---|---|
| 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 |
2688 | 2844 | |
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. |
|---|---|---|---|---|
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 28, 2023 | RCV002796286.4 |
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
(Mar 28, 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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Myriad Genetics, Inc.
Accession: SCV004018947.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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Pathogenic
(May 11, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003201873.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu195Argfs*58) 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.Glu195Argfs*58) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
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Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Glu195Argfs*58) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. For these reasons, this variant has been classified as Pathogenic.
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. |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Comment:
This sequence change creates a premature translational stop signal (p.Glu195Argfs*58) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
HelpText-mined citations for this variant ...
HelpRecord last updated Sep 29, 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.