The c.1645delC (p.Q549Sfs*22) variant, located in coding exon 16 of the MUTYH gene causes a translational frameshift and an extension of the protein by 20 amino acids. This alteration occurs at the 3' terminus of theMUTYH gene and is not expected to trigger nonsense-mediated mRNAdecay. A different variant which results in a similarly elongated protein has been detected in a biallelic state in multiple patients with polyposis (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.1561del (p.Gln521fs)
Germline
Classification
Help
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.
(1)
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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.
Likely pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001048174.2(MUTYH):c.1561del (p.Gln521fs)
Variation ID: 1777140 Accession: VCV001777140.2
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 1p34.1 1: 45329311 (GRCh38) [ NCBI UCSC ] 1: 45794983 (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 Nov 29, 2022 May 1, 2024 Nov 19, 2020 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001048174.2:c.1561del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001041639.1:p.Gln521fs frameshift NM_001128425.2:c.1645del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Gln549fs frameshift NM_001048171.2:c.1561del NP_001041636.2:p.Gln521fs frameshift NM_001048172.2:c.1564del NP_001041637.1:p.Gln522fs frameshift NM_001048173.2:c.1561del NP_001041638.1:p.Gln521fs frameshift NM_001128425.1:c.1645delC frameshift NM_001293190.2:c.1606del NP_001280119.1:p.Gln536fs frameshift NM_001293191.2:c.1594del NP_001280120.1:p.Gln532fs frameshift NM_001293192.2:c.1285del NP_001280121.1:p.Gln429fs frameshift NM_001293195.2:c.1561del NP_001280124.1:p.Gln521fs frameshift NM_001293196.2:c.1285del NP_001280125.1:p.Gln429fs frameshift NM_001350650.2:c.1216del NP_001337579.1:p.Gln406fs frameshift NM_001350651.2:c.1216del NP_001337580.1:p.Gln406fs frameshift NM_001407069.1:c.1592delC NP_001393998.1:p.Gln532Serfs frameshift NM_001407070.1:c.1559delC NP_001393999.1:p.Gln521Serfs frameshift NM_001407071.1:c.1562delC NP_001394000.1:p.Gln522Serfs frameshift NM_001407072.1:c.1559delC NP_001394001.1:p.Gln521Serfs frameshift NM_001407073.1:c.1559delC NP_001394002.1:p.Gln521Serfs frameshift NM_001407075.1:c.1475delC NP_001394004.1:p.Gln493Serfs frameshift NM_001407077.1:c.1592delC NP_001394006.1:p.Gln532Serfs frameshift NM_001407078.1:c.1562delC NP_001394007.1:p.Gln522Serfs frameshift NM_001407079.1:c.1520delC NP_001394008.1:p.Gln508Serfs frameshift NM_001407080.1:c.1517delC NP_001394009.1:p.Gln507Serfs frameshift NM_001407081.1:c.1559delC NP_001394010.1:p.Gln521Serfs frameshift NM_001407082.1:c.1214delC NP_001394011.1:p.Gln406Serfs frameshift NM_001407083.1:c.1601delC NP_001394012.1:p.Gln535Serfs frameshift NM_001407085.1:c.1601delC NP_001394014.1:p.Gln535Serfs frameshift NM_001407086.1:c.1562delC NP_001394015.1:p.Gln522Serfs frameshift NM_001407087.1:c.1580delC NP_001394016.1:p.Gln528Serfs frameshift NM_001407088.1:c.1559delC NP_001394017.1:p.Gln521Serfs frameshift NM_001407089.1:c.1559delC NP_001394018.1:p.Gln521Serfs frameshift NM_001407091.1:c.1283delC NP_001394020.1:p.Gln429Serfs frameshift NM_012222.3:c.1636del NP_036354.1:p.Gln546fs frameshift NR_146882.2:n.1969del non-coding transcript variant NR_146883.2:n.1818del non-coding transcript variant NR_176269.1:n.1963delC NR_176270.1:n.1903delC NR_176271.1:n.1826delC NR_176272.1:n.1890delC NR_176273.1:n.1848delC NR_176274.1:n.1903delC NC_000001.11:g.45329313del NC_000001.10:g.45794985del NG_008189.1:g.16160del LRG_220:g.16160del LRG_220t1:c.1643del LRG_220p1:p.Gln549Serfs - Protein change
- Q522fs, Q549fs, Q546fs, Q406fs, Q429fs, Q521fs, Q536fs, Q532fs
- Other names
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- Canonical SPDI
- NC_000001.11:45329310:GGG:GG
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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
Help
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
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
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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Nov 19, 2020 | RCV002394968.2 |
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
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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Likely pathogenic
(Nov 19, 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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Ambry Genetics
Accession: SCV002703420.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.1645delC (p.Q549Sfs*22) variant, located in coding exon 16 of the MUTYH gene causes a translational frameshift and an extension of the protein by 20 … (more)
The c.1645delC (p.Q549Sfs*22) variant, located in coding exon 16 of the MUTYH gene causes a translational frameshift and an extension of the protein by 20 amino acids. This alteration occurs at the 3' terminus of theMUTYH gene and is not expected to trigger nonsense-mediated mRNAdecay. A different variant which results in a similarly elongated protein has been detected in a biallelic state in multiple patients with polyposis (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
|
Comment:
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. |
Comment:
The c.1645delC (p.Q549Sfs*22) variant, located in coding exon 16 of the MUTYH gene causes a translational frameshift and an extension of the protein by 20 amino acids. This alteration occurs at the 3' terminus of theMUTYH gene and is not expected to trigger nonsense-mediated mRNAdecay. A different variant which results in a similarly elongated protein has been detected in a biallelic state in multiple patients with polyposis (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Citations for germline classification of this variant
Help| There 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 this variant ...
HelpRecord last updated May 01, 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.