ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.1405dup (p.Tyr469fs)
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.1405dup (p.Tyr469fs)
Variation ID: 1958675 Accession: VCV001958675.3
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 1p34.1 1: 45330544-45330545 (GRCh38) [ NCBI UCSC ] 1: 45796216-45796217 (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 7, 2023 Feb 28, 2024 Dec 21, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001048174.2:c.1405dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001041639.1:p.Tyr469fs frameshift NM_001128425.2:c.1489dup MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Tyr497fs frameshift NM_001048171.2:c.1405dup NP_001041636.2:p.Tyr469fs frameshift NM_001048172.2:c.1408dup NP_001041637.1:p.Tyr470fs frameshift NM_001048173.2:c.1405dup NP_001041638.1:p.Tyr469fs frameshift NM_001293190.2:c.1450dup NP_001280119.1:p.Tyr484fs frameshift NM_001293191.2:c.1438dup NP_001280120.1:p.Tyr480fs frameshift NM_001293192.2:c.1129dup NP_001280121.1:p.Tyr377fs frameshift NM_001293195.2:c.1405dup NP_001280124.1:p.Tyr469fs frameshift NM_001293196.2:c.1129dup NP_001280125.1:p.Tyr377fs frameshift NM_001350650.2:c.1060dup NP_001337579.1:p.Tyr354fs frameshift NM_001350651.2:c.1060dup NP_001337580.1:p.Tyr354fs frameshift NM_001407069.1:c.1438dup NP_001393998.1:p.Tyr480Leufs frameshift NM_001407070.1:c.1405dup NP_001393999.1:p.Tyr469Leufs frameshift NM_001407071.1:c.1408dup NP_001394000.1:p.Tyr470Leufs frameshift NM_001407072.1:c.1405dup NP_001394001.1:p.Tyr469Leufs frameshift NM_001407073.1:c.1405dup NP_001394002.1:p.Tyr469Leufs frameshift NM_001407075.1:c.1321dup NP_001394004.1:p.Tyr441Leufs frameshift NM_001407077.1:c.1438dup NP_001394006.1:p.Tyr480Leufs frameshift NM_001407078.1:c.1408dup NP_001394007.1:p.Tyr470Leufs frameshift NM_001407079.1:c.1366dup NP_001394008.1:p.Tyr456Leufs frameshift NM_001407080.1:c.1363dup NP_001394009.1:p.Tyr455Leufs frameshift NM_001407081.1:c.1405dup NP_001394010.1:p.Tyr469Leufs frameshift NM_001407082.1:c.1060dup NP_001394011.1:p.Tyr354Leufs frameshift NM_001407083.1:c.1447dup NP_001394012.1:p.Tyr483Leufs frameshift NM_001407085.1:c.1447dup NP_001394014.1:p.Tyr483Leufs frameshift NM_001407086.1:c.1408dup NP_001394015.1:p.Tyr470Leufs frameshift NM_001407087.1:c.1426dup NP_001394016.1:p.Tyr476Leufs frameshift NM_001407088.1:c.1405dup NP_001394017.1:p.Tyr469Leufs frameshift NM_001407089.1:c.1405dup NP_001394018.1:p.Tyr469Leufs frameshift NM_001407091.1:c.1129dup NP_001394020.1:p.Tyr377Leufs frameshift NM_012222.3:c.1480dup NP_036354.1:p.Tyr494fs frameshift NR_146882.2:n.1633dup non-coding transcript variant NR_146883.2:n.1482dup non-coding transcript variant NR_176269.1:n.1629dup NR_176270.1:n.1569dup NR_176271.1:n.1492dup NR_176272.1:n.1556dup NR_176273.1:n.1514dup NR_176274.1:n.1569dup NC_000001.11:g.45330545dup NC_000001.10:g.45796217dup NG_008189.1:g.14926dup LRG_220:g.14926dup LRG_220t1:c.1489dup LRG_220p1:p.Tyr497Leufs - Protein change
- Y470fs, Y354fs, Y377fs, Y469fs, Y497fs, Y484fs, Y480fs, Y494fs
- Other names
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- Canonical SPDI
- NC_000001.11:45330544: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
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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
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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
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
2565 | 2715 |
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
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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 (1) |
criteria provided, single submitter
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Dec 21, 2021 | RCV002725584.2 |
Submissions - Germline
Classification
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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
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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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Likely pathogenic
(Dec 21, 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:
germline
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Invitae
Accession: SCV002998860.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 28, 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 conserved PCNA binding motif of the MUTYH protein, which has been shown to be critical for MUTYH-PCNA binding and repair efficiency (PMID: 11092888, 26377631, 11433026, 11864576). While functional studies have not been performed to directly test the effect of this variant on MUTYH protein function, this suggests that disruption of this region of the protein is causative of disease. This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr497Leufs*35) in the MUTYH gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 53 amino acid(s) of the MUTYH protein. (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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Distinct functional consequences of MUTYH variants associated with colorectal cancer: Damaged DNA affinity, glycosylase activity and interaction with PCNA and Hus1. | Brinkmeyer MK | DNA repair | 2015 | PMID: 26377631 |
Replication-associated repair of adenine:8-oxoguanine mispairs by MYH. | Hayashi H | Current biology : CB | 2002 | PMID: 11864576 |
hMYH cell cycle-dependent expression, subcellular localization and association with replication foci: evidence suggesting replication-coupled repair of adenine:8-oxoguanine mispairs. | Boldogh I | Nucleic acids research | 2001 | PMID: 11433026 |
Human homolog of the MutY repair protein (hMYH) physically interacts with proteins involved in long patch DNA base excision repair. | Parker A | The Journal of biological chemistry | 2001 | PMID: 11092888 |
Text-mined citations for this variant ...
HelpRecord last updated Feb 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.