ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.1016_1017del (p.Pro339fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001048174.2(MUTYH):c.1016_1017del (p.Pro339fs)
Variation ID: 406858 Accession: VCV000406858.7
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 1p34.1 1: 45331746-45331747 (GRCh38) [ NCBI UCSC ] 1: 45797418-45797419 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 10, 2018 Feb 20, 2024 May 27, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001048174.2:c.1016_1017del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001041639.1:p.Pro339fs frameshift NM_001128425.2:c.1100_1101del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Pro367fs frameshift NM_001048171.2:c.1016_1017del NP_001041636.2:p.Pro339fs frameshift NM_001048172.2:c.1019_1020del NP_001041637.1:p.Pro340fs frameshift NM_001048173.2:c.1016_1017del NP_001041638.1:p.Pro339fs frameshift NM_001128425.1:c.1100_1101delCC NM_001293190.2:c.1061_1062del NP_001280119.1:p.Pro354fs frameshift NM_001293191.2:c.1049_1050del NP_001280120.1:p.Pro350fs frameshift NM_001293192.2:c.740_741del NP_001280121.1:p.Pro247fs frameshift NM_001293195.2:c.1016_1017del NP_001280124.1:p.Pro339fs frameshift NM_001293196.2:c.740_741del NP_001280125.1:p.Pro247fs frameshift NM_001350650.2:c.671_672del NP_001337579.1:p.Pro224fs frameshift NM_001350651.2:c.671_672del NP_001337580.1:p.Pro224fs frameshift NM_012222.3:c.1091_1092del NP_036354.1:p.Pro364fs frameshift NR_146882.2:n.1244_1245del non-coding transcript variant NR_146883.2:n.1093_1094del non-coding transcript variant NC_000001.11:g.45331750_45331751del NC_000001.10:g.45797422_45797423del NG_008189.1:g.13724_13725del LRG_220:g.13724_13725del - Protein change
- P339fs, P350fs, P340fs, P354fs, P364fs, P224fs, P247fs, P367fs
- Other names
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- Canonical SPDI
- NC_000001.11:45331745:GGGGGG:GGGG
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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
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MUTYH | - | - |
GRCh38 GRCh37 |
2566 | 2714 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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May 27, 2022 | RCV000474499.8 |
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
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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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Likely pathogenic
(Jan 09, 2020)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000545785.6
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
Comment:
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has … (more)
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Glu480 and p.Val493 amino acid residues in MUTYH. Other variants that disrupt these residues have been determined to be pathogenic (PMID: 14999774, 15635083, 12707038, 16557584, 17949294, 17931073). This suggests that these residues are clinically significant, and that variants that disrupt these residues are likely to be disease-causing. This variant has not been reported in the literature in individuals with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 406858). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the MUTYH gene (p.Pro367Glnfs*164). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 183 amino acids of the MUTYH protein. (less)
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Likely pathogenic
(May 27, 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:
unknown
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Baylor Genetics
Accession: SCV004199426.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Similar colorectal cancer risk in patients with monoallelic and biallelic mutations in the MYH gene identified in a population with adenomatous polyposis. | Olschwang S | Genetic testing | 2007 | PMID: 17949294 |
The thorough screening of the MUTYH gene in a large French cohort of sporadic colorectal cancers. | Küry S | Genetic testing | 2007 | PMID: 17931073 |
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 |
The potential for increased clinical sensitivity in genetic testing for polyposis colorectal cancer through the analysis of MYH mutations in North American patients. | Eliason K | Journal of medical genetics | 2005 | PMID: 15635083 |
Prevalence of the Y165C, G382D and 1395delGGA germline mutations of the MYH gene in Italian patients with adenomatous polyposis coli and colorectal adenomas. | Gismondi V | International journal of cancer | 2004 | PMID: 14999774 |
Germline mutations but not somatic changes at the MYH locus contribute to the pathogenesis of unselected colorectal cancers. | Halford SE | The American journal of pathology | 2003 | PMID: 12707038 |
Text-mined citations for rs768130289 ...
HelpRecord last updated Feb 20, 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.