ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.1253_1255del (p.Phe418del)
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.1253_1255del (p.Phe418del)
Variation ID: 492014 Accession: VCV000492014.19
- Type and length
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Deletion, 3 bp
- Location
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Cytogenetic: 1p34.1 1: 45331319-45331321 (GRCh38) [ NCBI UCSC ] 1: 45796991-45796993 (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 19, 2018 May 1, 2024 Feb 9, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001048174.2:c.1253_1255del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001041639.1:p.Phe418del inframe deletion NM_001128425.2:c.1337_1339del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Phe446del inframe deletion NM_001048171.2:c.1253_1255del NP_001041636.2:p.Phe418del inframe deletion NM_001048172.2:c.1256_1258del NP_001041637.1:p.Phe419del inframe deletion NM_001048173.2:c.1253_1255del NP_001041638.1:p.Phe418del inframe deletion NM_001128425.1:c.1337_1339delTCT NM_001293190.2:c.1298_1300del NP_001280119.1:p.Phe433del inframe deletion NM_001293191.2:c.1286_1288del NP_001280120.1:p.Phe429del inframe deletion NM_001293192.2:c.977_979del NP_001280121.1:p.Phe326del inframe deletion NM_001293195.2:c.1253_1255del NP_001280124.1:p.Phe418del inframe deletion NM_001293196.2:c.977_979del NP_001280125.1:p.Phe326del inframe deletion NM_001350650.2:c.908_910del NP_001337579.1:p.Phe303del inframe deletion NM_001350651.2:c.908_910del NP_001337580.1:p.Phe303del inframe deletion NM_012222.3:c.1328_1330del NP_036354.1:p.Phe443del inframe deletion NR_146882.2:n.1481_1483del non-coding transcript variant NR_146883.2:n.1330_1332del non-coding transcript variant NC_000001.11:g.45331321_45331323del NC_000001.10:g.45796993_45796995del NG_008189.1:g.14150_14152del LRG_220:g.14150_14152del LRG_220t1:c.1337_1339del LRG_220p1:p.Phe446del - Protein change
- F446del, F326del, F418del, F303del, F419del, F429del, F443del, F433del
- Other names
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- Canonical SPDI
- NC_000001.11:45331318:AGAAG:AG
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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
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 |
2688 | 2844 |
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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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Feb 9, 2024 | RCV000584316.8 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Oct 26, 2023 | RCV000640372.9 | |
Uncertain significance (1) |
criteria provided, single submitter
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Dec 19, 2019 | RCV001755974.2 |
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
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
Help
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
(Jan 03, 2020)
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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: SCV000690521.4
First in ClinVar: Feb 19, 2018 Last updated: Jan 12, 2022 |
Comment:
This variant causes the deletion of a single amino acid, phenylalanine 446, in the MUTYH protein. This variant is also known as c.1295_1297del (p.Phe432del) based … (more)
This variant causes the deletion of a single amino acid, phenylalanine 446, in the MUTYH protein. This variant is also known as c.1295_1297del (p.Phe432del) based on an alternative transcript (NM_001048171). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251496 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Dec 19, 2019)
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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: SCV001997353.2
First in ClinVar: Nov 06, 2021 Last updated: Mar 04, 2023 |
Comment:
In-frame deletion of 1 amino acid in a non-repeat region; Located in a critical functional domain: NUDIX domain (Ruggieri 2013); Has not been previously published … (more)
In-frame deletion of 1 amino acid in a non-repeat region; Located in a critical functional domain: NUDIX domain (Ruggieri 2013); Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek 2016) (less)
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Uncertain significance
(Oct 26, 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:
unknown
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Baylor Genetics
Accession: SCV004198800.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Uncertain significance
(Oct 13, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000761961.6
First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant, c.1337_1339del, results in the deletion of 1 amino acid(s) of the MUTYH protein (p.Phe446del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.1337_1339del, results in the deletion of 1 amino acid(s) of the MUTYH protein (p.Phe446del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs747232389, gnomAD 0.003%). This variant has been observed in individual(s) with clinical features of MUTYH-associated polyposis (Invitae). ClinVar contains an entry for this variant (Variation ID: 492014). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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
(Feb 09, 2024)
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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: SCV001171085.4
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The c.1337_1339delTCT variant (also known as p.F446del) is located in coding exon 14 of the MUTYH gene. This variant results from an in-frame TCT deletion … (more)
The c.1337_1339delTCT variant (also known as p.F446del) is located in coding exon 14 of the MUTYH gene. This variant results from an in-frame TCT deletion at nucleotide positions 1337 to 1339. This results in the in-frame deletion of a phenylalanine at codon 446. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, 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 rs747232389 ...
HelpRecord last updated Sep 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.