ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.1196_1205del (p.Trp399fs)
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.1196_1205del (p.Trp399fs)
Variation ID: 533306 Accession: VCV000533306.8
- Type and length
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Deletion, 10 bp
- Location
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Cytogenetic: 1p34.1 1: 45331454-45331463 (GRCh38) [ NCBI UCSC ] 1: 45797126-45797135 (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 May 28, 2018 Feb 14, 2024 Sep 2, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001048174.2:c.1196_1205del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001041639.1:p.Trp399fs frameshift NM_001128425.2:c.1280_1289del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Trp427fs frameshift NM_001048171.2:c.1196_1205del NP_001041636.2:p.Trp399fs frameshift NM_001048172.2:c.1199_1208del NP_001041637.1:p.Trp400fs frameshift NM_001048173.2:c.1196_1205del NP_001041638.1:p.Trp399fs frameshift NM_001128425.1:c.1280_1289del10 NM_001128425.1:c.1280_1289delGGGCTGGGCC NM_001293190.2:c.1241_1250del NP_001280119.1:p.Trp414fs frameshift NM_001293191.2:c.1229_1238del NP_001280120.1:p.Trp410fs frameshift NM_001293192.2:c.920_929del NP_001280121.1:p.Trp307fs frameshift NM_001293195.2:c.1196_1205del NP_001280124.1:p.Trp399fs frameshift NM_001293196.2:c.920_929del NP_001280125.1:p.Trp307fs frameshift NM_001350650.2:c.851_860del NP_001337579.1:p.Trp284fs frameshift NM_001350651.2:c.851_860del NP_001337580.1:p.Trp284fs frameshift NM_012222.3:c.1271_1280del NP_036354.1:p.Trp424fs frameshift NR_146882.2:n.1424_1433del non-coding transcript variant NR_146883.2:n.1273_1282del non-coding transcript variant NC_000001.11:g.45331454_45331463del NC_000001.10:g.45797126_45797135del NG_008189.1:g.14008_14017del LRG_220:g.14008_14017del LRG_220t1:c.1280_1289del10 - Protein change
- W307fs, W284fs, W400fs, W410fs, W414fs, W424fs, W399fs, W427fs
- Other names
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- Canonical SPDI
- NC_000001.11:45331453:GGCCCAGCCC:
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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
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
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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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Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Aug 7, 2023 | RCV000640364.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 2, 2023 | RCV003352961.1 |
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
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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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Pathogenic
(Sep 02, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV004055766.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
The c.1280_1289del10 pathogenic mutation, located in coding exon 13 of the MUTYH gene, results from a deletion of 10 nucleotides at nucleotide positions 1280 to … (more)
The c.1280_1289del10 pathogenic mutation, located in coding exon 13 of the MUTYH gene, results from a deletion of 10 nucleotides at nucleotide positions 1280 to 1289, causing a translational frameshift with a predicted alternate stop codon (p.W427Sfs*22). This alteration has been previously identified in an individual from a North American cohort of individuals with early onset colon cancer (Pearlman R et al. JAMA Oncol, 2017 Apr;3:464-471). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Likely pathogenic
(Oct 19, 2021)
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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: SCV004199437.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Aug 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000761953.4
First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024 |
Comment:
ClinVar contains an entry for this variant (Variation ID: 533306). This sequence change creates a premature translational stop signal (p.Trp427Serfs*22) in the MUTYH gene. It … (more)
ClinVar contains an entry for this variant (Variation ID: 533306). This sequence change creates a premature translational stop signal (p.Trp427Serfs*22) 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 premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 27978560). For these reasons, this variant has been classified as Pathogenic. (less)
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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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Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer. | Pearlman R | JAMA oncology | 2017 | PMID: 27978560 |
MUTYH-associated polyposis (MAP). | Nielsen M | Critical reviews in oncology/hematology | 2011 | PMID: 20663686 |
Characterization of mutant MUTYH proteins associated with familial colorectal cancer. | Ali M | Gastroenterology | 2008 | PMID: 18534194 |
Text-mined citations for rs1553125677 ...
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.