The c.638delC pathogenic mutation, located in coding exon 8 of the MUTYH gene, results from a deletion of one nucleotide at nucleotide position 638, causing a translational frameshift with a predicted alternate stop codon (p.P213Lfs*27). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.554del (p.Pro185fs)
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.
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.554del (p.Pro185fs)
Variation ID: 1753221 Accession: VCV001753221.2
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 1p34.1 1: 45332626 (GRCh38) [ NCBI UCSC ] 1: 45798298 (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 Feb 15, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001048174.2:c.554del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001041639.1:p.Pro185fs frameshift NM_001128425.2:c.638del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121897.1:p.Pro213fs frameshift NM_001048171.2:c.554del NP_001041636.2:p.Pro185fs frameshift NM_001048172.2:c.557del NP_001041637.1:p.Pro186fs frameshift NM_001048173.2:c.554del NP_001041638.1:p.Pro185fs frameshift NM_001128425.1:c.638delC frameshift NM_001293190.2:c.599del NP_001280119.1:p.Pro200fs frameshift NM_001293191.2:c.587del NP_001280120.1:p.Pro196fs frameshift NM_001293192.2:c.278del NP_001280121.1:p.Pro93fs frameshift NM_001293195.2:c.554del NP_001280124.1:p.Pro185fs frameshift NM_001293196.2:c.278del NP_001280125.1:p.Pro93fs frameshift NM_001350650.2:c.209del NP_001337579.1:p.Pro70fs frameshift NM_001350651.2:c.209del NP_001337580.1:p.Pro70fs frameshift NM_001407069.1:c.586delC NP_001393998.1:p.Pro196Leufs frameshift NM_001407070.1:c.553delC NP_001393999.1:p.Pro185Leufs frameshift NM_001407071.1:c.556delC NP_001394000.1:p.Pro186Leufs frameshift NM_001407072.1:c.553delC NP_001394001.1:p.Pro185Leufs frameshift NM_001407073.1:c.553delC NP_001394002.1:p.Pro185Leufs frameshift NM_001407075.1:c.469delC NP_001394004.1:p.Pro157Leufs frameshift NM_001407077.1:c.586delC NP_001394006.1:p.Pro196Leufs frameshift NM_001407078.1:c.556delC NP_001394007.1:p.Pro186Leufs frameshift NM_001407079.1:c.514delC NP_001394008.1:p.Pro172Leufs frameshift NM_001407080.1:c.511delC NP_001394009.1:p.Pro171Leufs frameshift NM_001407081.1:c.553delC NP_001394010.1:p.Pro185Leufs frameshift NM_001407082.1:c.208delC NP_001394011.1:p.Pro70Leufs frameshift NM_001407083.1:c.595delC NP_001394012.1:p.Pro199Leufs frameshift NM_001407085.1:c.595delC NP_001394014.1:p.Pro199Leufs frameshift NM_001407086.1:c.556delC NP_001394015.1:p.Pro186Leufs frameshift NM_001407087.1:c.574delC NP_001394016.1:p.Pro192Leufs frameshift NM_001407088.1:c.553delC NP_001394017.1:p.Pro185Leufs frameshift NM_001407089.1:c.553delC NP_001394018.1:p.Pro185Leufs frameshift NM_001407091.1:c.277delC NP_001394020.1:p.Pro93Leufs frameshift NM_012222.3:c.629del NP_036354.1:p.Pro210fs frameshift NR_146882.2:n.782del non-coding transcript variant NR_146883.2:n.631del non-coding transcript variant NR_176269.1:n.777delC NR_176270.1:n.717delC NR_176271.1:n.640delC NR_176272.1:n.704delC NR_176273.1:n.662delC NR_176274.1:n.717delC NC_000001.11:g.45332627del NC_000001.10:g.45798299del NG_008189.1:g.12845del LRG_220:g.12845del LRG_220t1:c.637del LRG_220p1:p.Pro213Leufs - Protein change
- P186fs, P200fs, P196fs, P210fs, P213fs, P185fs, P70fs, P93fs
- Other names
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- Canonical SPDI
- NC_000001.11:45332625:GG:G
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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. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
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Feb 15, 2022 | RCV002369142.2 |
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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Pathogenic
(Feb 15, 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: SCV002659115.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.638delC pathogenic mutation, located in coding exon 8 of the MUTYH gene, results from a deletion of one nucleotide at nucleotide position 638, causing … (more)
The c.638delC pathogenic mutation, located in coding exon 8 of the MUTYH gene, results from a deletion of one nucleotide at nucleotide position 638, causing a translational frameshift with a predicted alternate stop codon (p.P213Lfs*27). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (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.638delC pathogenic mutation, located in coding exon 8 of the MUTYH gene, results from a deletion of one nucleotide at nucleotide position 638, causing a translational frameshift with a predicted alternate stop codon (p.P213Lfs*27). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
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.