This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.1370del (p.Ser457fs)
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.
(3)
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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
3
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000038.6(APC):c.1370del (p.Ser457fs)
Variation ID: 2203681 Accession: VCV002203681.5
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 5q22.2 5: 112821953 (GRCh38) [ NCBI UCSC ] 5: 112157650 (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 Aug 11, 2024 Apr 25, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000038.6:c.1370del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Ser457fs frameshift NM_000038.5:c.1370delC NM_001127510.3:c.1370del NP_001120982.1:p.Ser457fs frameshift NM_001127511.3:c.1316del NP_001120983.2:p.Ser439fs frameshift NM_001354895.2:c.1370del NP_001341824.1:p.Ser457fs frameshift NM_001354896.2:c.1370del NP_001341825.1:p.Ser457fs frameshift NM_001354897.2:c.1400del NP_001341826.1:p.Ser467fs frameshift NM_001354898.2:c.1295del NP_001341827.1:p.Ser432fs frameshift NM_001354899.2:c.1286del NP_001341828.1:p.Ser429fs frameshift NM_001354900.2:c.1193del NP_001341829.1:p.Ser398fs frameshift NM_001354901.2:c.1193del NP_001341830.1:p.Ser398fs frameshift NM_001354902.2:c.1097del NP_001341831.1:p.Ser366fs frameshift NM_001354903.2:c.1067del NP_001341832.1:p.Ser356fs frameshift NM_001354904.2:c.992del NP_001341833.1:p.Ser331fs frameshift NM_001354905.2:c.890del NP_001341834.1:p.Ser297fs frameshift NM_001354906.2:c.521del NP_001341835.1:p.Ser174fs frameshift NM_001407446.1:c.1400delC NP_001394375.1:p.Ser467Tyrfs frameshift NM_001407447.1:c.1370delC NP_001394376.1:p.Ser457Tyrfs frameshift NM_001407448.1:c.1370delC NP_001394377.1:p.Ser457Tyrfs frameshift NM_001407449.1:c.1370delC NP_001394378.1:p.Ser457Tyrfs frameshift NM_001407450.1:c.1370delC NP_001394379.1:p.Ser457Tyrfs frameshift NM_001407451.1:c.1295delC NP_001394380.1:p.Ser432Tyrfs frameshift NM_001407452.1:c.1286delC NP_001394381.1:p.Ser429Tyrfs frameshift NM_001407453.1:c.1193delC NP_001394382.1:p.Ser398Tyrfs frameshift NM_001407454.1:c.1067delC NP_001394383.1:p.Ser356Tyrfs frameshift NM_001407455.1:c.1067delC NP_001394384.1:p.Ser356Tyrfs frameshift NM_001407456.1:c.1067delC NP_001394385.1:p.Ser356Tyrfs frameshift NM_001407457.1:c.1067delC NP_001394386.1:p.Ser356Tyrfs frameshift NM_001407458.1:c.1067delC NP_001394387.1:p.Ser356Tyrfs frameshift NM_001407459.1:c.1067delC NP_001394388.1:p.Ser356Tyrfs frameshift NM_001407460.1:c.1067delC NP_001394389.1:p.Ser356Tyrfs frameshift NM_001407467.1:c.983delC NP_001394396.1:p.Ser328Tyrfs frameshift NM_001407469.1:c.983delC NP_001394398.1:p.Ser328Tyrfs frameshift NM_001407470.1:c.521delC NP_001394399.1:p.Ser174Tyrfs frameshift NM_001407471.1:c.218delC NP_001394400.1:p.Ser73Tyrfs frameshift NM_001407472.1:c.218delC NP_001394401.1:p.Ser73Tyrfs frameshift NR_176365.1:n.1540delC NR_176366.1:n.1959delC NC_000005.10:g.112821953del NC_000005.9:g.112157650del NG_008481.4:g.134433del LRG_130:g.134433del LRG_130t1:c.1370del LRG_130p1:p.Ser457Tyrfs LRG_130t2:c.1370del LRG_130p2:p.Ser457Tyrfs LRG_130t3:c.1370del LRG_130p3:p.Ser457Tyrfs - Protein change
- S174fs, S297fs, S398fs, S331fs, S432fs, S457fs, S356fs, S366fs, S429fs, S439fs, S467fs
- Other names
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- Canonical SPDI
- NC_000005.10:112821952:C:
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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 | ||
|---|---|---|---|---|---|---|
| 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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| APC | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
14969 | 15107 | |
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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Apr 25, 2024 | RCV004654167.1 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jun 29, 2023 | RCV004565734.2 |
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
(May 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004043813.2
First in ClinVar: Oct 21, 2023 Last updated: Oct 28, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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Pathogenic
(Jun 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003525934.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
ClinVar contains an entry for this variant (Variation ID: 2203681). This premature translational stop signal has been observed in individual(s) with hereditary colorectal polyposis/cancers (PMID: … (more)
ClinVar contains an entry for this variant (Variation ID: 2203681). This premature translational stop signal has been observed in individual(s) with hereditary colorectal polyposis/cancers (PMID: 26837502). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser457Tyrfs*10) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Apr 25, 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: SCV005148616.1
First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024 |
Comment:
The c.1370delC pathogenic mutation, located in coding exon 10 of the APC gene, results from a deletion of one nucleotide at nucleotide position 1370, causing … (more)
The c.1370delC pathogenic mutation, located in coding exon 10 of the APC gene, results from a deletion of one nucleotide at nucleotide position 1370, causing a translational frameshift with a predicted alternate stop codon (p.S457Yfs*10). This variant has been observed in at least one individual with a personal and/or family history that is consistent with familial adenomatous polyposis (FAP) (Ambry internal data). 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)
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Comment:
Comment:
ClinVar contains an entry for this variant (Variation ID: 2203681). This premature translational stop signal has been observed in individual(s) with hereditary colorectal polyposis/cancers (PMID: 26837502). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser457Tyrfs*10) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). For these reasons, this variant has been classified as Pathogenic.
Comment:
The c.1370delC pathogenic mutation, located in coding exon 10 of the APC gene, results from a deletion of one nucleotide at nucleotide position 1370, causing a translational frameshift with a predicted alternate stop codon (p.S457Yfs*10). This variant has been observed in at least one individual with a personal and/or family history that is consistent with familial adenomatous polyposis (FAP) (Ambry internal data). 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.
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:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Comment:
ClinVar contains an entry for this variant (Variation ID: 2203681). This premature translational stop signal has been observed in individual(s) with hereditary colorectal polyposis/cancers (PMID: 26837502). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser457Tyrfs*10) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). For these reasons, this variant has been classified as Pathogenic.
Comment:
The c.1370delC pathogenic mutation, located in coding exon 10 of the APC gene, results from a deletion of one nucleotide at nucleotide position 1370, causing a translational frameshift with a predicted alternate stop codon (p.S457Yfs*10). This variant has been observed in at least one individual with a personal and/or family history that is consistent with familial adenomatous polyposis (FAP) (Ambry internal data). 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| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Rapid detection of germline mutations for hereditary gastrointestinal polyposis/cancers using HaloPlex target enrichment and high-throughput sequencing technologies. | Kohda M | Familial cancer | 2016 | PMID: 26837502 |
| Germline APC mutation spectrum derived from 863 genomic variations identified through a 15-year medical genetics service to French patients with FAP. | Lagarde A | Journal of medical genetics | 2010 | PMID: 20685668 |
| Mutational screening of the APC gene in Chilean families with familial adenomatous polyposis: nine novel truncating mutations. | De la Fuente MK | Diseases of the colon and rectum | 2007 | PMID: 17963004 |
Text-mined citations for this variant ...
HelpRecord last updated Nov 10, 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.