ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.1393G>A (p.Val465Ile)
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.1393G>A (p.Val465Ile)
Variation ID: 142092 Accession: VCV000142092.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p34.1 1: 45330557 (GRCh38) [ NCBI UCSC ] 1: 45796229 (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 Jun 1, 2016 May 1, 2024 Aug 11, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001048174.2:c.1393G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001041639.1:p.Val465Ile missense NM_001128425.2:c.1477G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Val493Ile missense NM_001048171.2:c.1393G>A NP_001041636.2:p.Val465Ile missense NM_001048172.2:c.1396G>A NP_001041637.1:p.Val466Ile missense NM_001048173.2:c.1393G>A NP_001041638.1:p.Val465Ile missense NM_001293190.2:c.1438G>A NP_001280119.1:p.Val480Ile missense NM_001293191.2:c.1426G>A NP_001280120.1:p.Val476Ile missense NM_001293192.2:c.1117G>A NP_001280121.1:p.Val373Ile missense NM_001293195.2:c.1393G>A NP_001280124.1:p.Val465Ile missense NM_001293196.2:c.1117G>A NP_001280125.1:p.Val373Ile missense NM_001350650.2:c.1048G>A NP_001337579.1:p.Val350Ile missense NM_001350651.2:c.1048G>A NP_001337580.1:p.Val350Ile missense NM_012222.3:c.1468G>A NP_036354.1:p.Val490Ile missense NR_146882.2:n.1621G>A non-coding transcript variant NR_146883.2:n.1470G>A non-coding transcript variant NC_000001.11:g.45330557C>T NC_000001.10:g.45796229C>T NG_008189.1:g.14914G>A LRG_220:g.14914G>A LRG_220t1:c.1477G>A LRG_220p1:p.Val493Ile - Protein change
- V493I, V350I, V466I, V480I, V465I, V476I, V490I, V373I
- Other names
- p.V493I:GTT>ATT
- Canonical SPDI
- NC_000001.11:45330556:C:T
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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
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 |
2685 | 2841 |
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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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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May 9, 2022 | RCV000130919.10 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Aug 11, 2023 | RCV000197197.10 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 27, 2018 | RCV000212720.2 |
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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Uncertain significance
(Nov 27, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000211392.10
First in ClinVar: Feb 24, 2015 Last updated: Apr 17, 2019 |
Comment:
This variant is denoted MUTYH c.1477G>A at the cDNA level, p.Val493Ile (V493I) at the protein level, and results in the change of a Valine to … (more)
This variant is denoted MUTYH c.1477G>A at the cDNA level, p.Val493Ile (V493I) at the protein level, and results in the change of a Valine to an Isoleucine (GTT>ATT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. MUTYH Val493Ile was not observed in large population cohorts (Lek 2016). This variant is located in the NUDIX domain (Ruggieri 2013). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether MUTYH Val493Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. Of note, MUTYH-Associated Polyposis (MAP) is a recessive condition associated with two MUTYH pathogenic variants on opposite chromosomes. (less)
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Uncertain significance
(Aug 11, 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: SCV000254704.8
First in ClinVar: Oct 11, 2015 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 493 of the MUTYH protein (p.Val493Ile). … (more)
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 493 of the MUTYH protein (p.Val493Ile). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 142092). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Mar 28, 2019)
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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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Color Diagnostics, LLC DBA Color Health
Accession: SCV001346233.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
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Uncertain Significance
(Jun 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004833407.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Number of individuals with the variant: 1
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Uncertain significance
(May 09, 2022)
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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: SCV000185829.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.V493I variant (also known as c.1477G>A), located in coding exon 15 of the MUTYH gene, results from a G to A substitution at nucleotide … (more)
The p.V493I variant (also known as c.1477G>A), located in coding exon 15 of the MUTYH gene, results from a G to A substitution at nucleotide position c.1477. This variant impacts the first base pair of coding exon 15. The valine at codon 493 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs587782228 ...
HelpRecord last updated Jun 23, 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.