ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.1003_1006dup (p.Arg336fs)
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.1003_1006dup (p.Arg336fs)
Variation ID: 2133907 Accession: VCV002133907.2
- Type and length
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Duplication, 4 bp
- Location
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Cytogenetic: 1p34.1 1: 45331756-45331757 (GRCh38) [ NCBI UCSC ] 1: 45797428-45797429 (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 May 4, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001048174.2:c.1003_1006dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001041639.1:p.Arg336fs frameshift NM_001128425.2:c.1087_1090dup MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Arg364fs frameshift NM_001048171.2:c.1003_1006dup NP_001041636.2:p.Arg336fs frameshift NM_001048172.2:c.1006_1009dup NP_001041637.1:p.Arg337fs frameshift NM_001048173.2:c.1003_1006dup NP_001041638.1:p.Arg336fs frameshift NM_001293190.2:c.1048_1051dup NP_001280119.1:p.Arg351fs frameshift NM_001293191.2:c.1036_1039dup NP_001280120.1:p.Arg347fs frameshift NM_001293192.2:c.727_730dup NP_001280121.1:p.Arg244fs frameshift NM_001293195.2:c.1003_1006dup NP_001280124.1:p.Arg336fs frameshift NM_001293196.2:c.727_730dup NP_001280125.1:p.Arg244fs frameshift NM_001350650.2:c.658_661dup NP_001337579.1:p.Arg221fs frameshift NM_001350651.2:c.658_661dup NP_001337580.1:p.Arg221fs frameshift NM_001407069.1:c.1033_1036dup NP_001393998.1:p.Arg347Glnfs frameshift NM_001407070.1:c.1000_1003dup NP_001393999.1:p.Arg336Glnfs frameshift NM_001407071.1:c.1003_1006dup NP_001394000.1:p.Arg337Glnfs frameshift NM_001407072.1:c.1000_1003dup NP_001394001.1:p.Arg336Glnfs frameshift NM_001407073.1:c.1000_1003dup NP_001394002.1:p.Arg336Glnfs frameshift NM_001407075.1:c.916_919dup NP_001394004.1:p.Arg308Glnfs frameshift NM_001407077.1:c.1033_1036dup NP_001394006.1:p.Arg347Glnfs frameshift NM_001407078.1:c.1003_1006dup NP_001394007.1:p.Arg337Glnfs frameshift NM_001407079.1:c.961_964dup NP_001394008.1:p.Arg323Glnfs frameshift NM_001407080.1:c.958_961dup NP_001394009.1:p.Arg322Glnfs frameshift NM_001407081.1:c.1000_1003dup NP_001394010.1:p.Arg336Glnfs frameshift NM_001407082.1:c.655_658dup NP_001394011.1:p.Arg221Glnfs frameshift NM_001407083.1:c.1042_1045dup NP_001394012.1:p.Arg350Glnfs frameshift NM_001407085.1:c.1042_1045dup NP_001394014.1:p.Arg350Glnfs frameshift NM_001407086.1:c.1003_1006dup NP_001394015.1:p.Arg337Glnfs frameshift NM_001407087.1:c.1021_1024dup NP_001394016.1:p.Arg343Glnfs frameshift NM_001407088.1:c.1000_1003dup NP_001394017.1:p.Arg336Glnfs frameshift NM_001407089.1:c.1000_1003dup NP_001394018.1:p.Arg336Glnfs frameshift NM_001407091.1:c.724_727dup NP_001394020.1:p.Arg244Glnfs frameshift NM_012222.3:c.1078_1081dup NP_036354.1:p.Arg361fs frameshift NR_146882.2:n.1231_1234dup non-coding transcript variant NR_146883.2:n.1080_1083dup non-coding transcript variant NR_176269.1:n.1224_1227dup NR_176270.1:n.1164_1167dup NR_176271.1:n.1087_1090dup NR_176272.1:n.1151_1154dup NR_176273.1:n.1109_1112dup NR_176274.1:n.1164_1167dup NC_000001.11:g.45331760_45331763dup NC_000001.10:g.45797432_45797435dup NG_008189.1:g.13711_13714dup LRG_220:g.13711_13714dup LRG_220t1:c.1084_1087dup LRG_220p1:p.Arg364Glnfs - Protein change
- R336fs, R361fs, R221fs, R337fs, R244fs, R351fs, R364fs, R347fs
- Other names
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- Canonical SPDI
- NC_000001.11:45331756:GGCTGGC:GGCTGGCTGGC
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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
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
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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 |
2740 | 2897 |
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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Pathogenic (1) |
criteria provided, single submitter
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May 4, 2022 | RCV003056413.3 |
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
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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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Pathogenic
(May 04, 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: SCV003347375.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg364Glnfs*169) in the MUTYH gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Arg364Glnfs*169) in the MUTYH gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 186 amino acid(s) of the MUTYH protein. 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. This variant disrupts a region of the MUTYH protein in which other variant(s) (p.Arg368Glnfs*164 ) have been determined to be pathogenic (PMID: 11092888, 11433026, 11864576, 16941501, 24953332, 26377631). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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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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 |
Prevalence of germline MUTYH mutations among Lynch-like syndrome patients. | Castillejo A | European journal of cancer (Oxford, England : 1990) | 2014 | PMID: 24953332 |
Low frequency of AXIN2 mutations and high frequency of MUTYH mutations in patients with multiple polyposis. | Lejeune S | Human mutation | 2006 | PMID: 16941501 |
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 Jan 13, 2025
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.