ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.350C>A (p.Ser117Ter)
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_000038.6(APC):c.350C>A (p.Ser117Ter)
Variation ID: 418932 Accession: VCV000418932.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q22.2 5: 112767318 (GRCh38) [ NCBI UCSC ] 5: 112103015 (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 Dec 19, 2017 May 1, 2024 Jan 27, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000038.6:c.350C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Ser117Ter nonsense NM_001127510.3:c.350C>A NP_001120982.1:p.Ser117Ter nonsense NM_001127511.3:c.380C>A NP_001120983.2:p.Ser127Ter nonsense NM_001354895.2:c.350C>A NP_001341824.1:p.Ser117Ter nonsense NM_001354896.2:c.350C>A NP_001341825.1:p.Ser117Ter nonsense NM_001354897.2:c.380C>A NP_001341826.1:p.Ser127Ter nonsense NM_001354898.2:c.275C>A NP_001341827.1:p.Ser92Ter nonsense NM_001354899.2:c.350C>A NP_001341828.1:p.Ser117Ter nonsense NM_001354900.2:c.173C>A NP_001341829.1:p.Ser58Ter nonsense NM_001354901.2:c.173C>A NP_001341830.1:p.Ser58Ter nonsense NM_001354902.2:c.380C>A NP_001341831.1:p.Ser127Ter nonsense NM_001354903.2:c.350C>A NP_001341832.1:p.Ser117Ter nonsense NM_001354904.2:c.275C>A NP_001341833.1:p.Ser92Ter nonsense NM_001354905.2:c.173C>A NP_001341834.1:p.Ser58Ter nonsense NM_001354906.2:c.-686C>A 5 prime UTR NC_000005.10:g.112767318C>A NC_000005.9:g.112103015C>A NG_008481.4:g.79798C>A LRG_130:g.79798C>A - Protein change
- S117*, S127*, S58*, S92*
- Other names
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- Canonical SPDI
- NC_000005.10:112767317:C:A
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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
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
14790 | 14927 |
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
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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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Pathogenic (1) |
criteria provided, single submitter
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Oct 18, 2017 | RCV000482015.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 16, 2021 | RCV000561431.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 10, 2022 | RCV001824795.9 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 27, 2024 | RCV002525784.11 |
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
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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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Pathogenic
(Oct 18, 2017)
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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: SCV000566355.5
First in ClinVar: Apr 27, 2017 Last updated: Dec 19, 2017 |
Comment:
This pathogenic variant is denoted APC c.350C>A at the cDNA level and p.Ser117Ter (S117X) at the protein level. The substitution creates a nonsense variant, which … (more)
This pathogenic variant is denoted APC c.350C>A at the cDNA level and p.Ser117Ter (S117X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with attenuated Familial Adenomatous Polyposis (Kerr 2013) and is considered pathogenic. (less)
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Pathogenic
(Jan 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial multiple polyposis syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002074167.1
First in ClinVar: Feb 12, 2022 Last updated: Feb 12, 2022 |
Comment:
Variant summary: APC c.350C>A (p.Ser117X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: APC c.350C>A (p.Ser117X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251476 control chromosomes (gnomAD). c.350C>A has been reported in the literature in individuals affected with Familial Adenomatous Polyposis (examples: Wu_2001, Kerr_2013 and Findlen_2021). These data indicate that the variant is associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Apr 25, 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: SCV004045531.2
First in ClinVar: Oct 21, 2023 Last updated: Oct 28, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
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Pathogenic
(Jan 27, 2024)
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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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Invitae
Accession: SCV000768277.8
First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ser117*) in the APC gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ser117*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with APC-related disease (PMID: 11960572, 23159591). ClinVar contains an entry for this variant (Variation ID: 418932). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Apr 16, 2021)
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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: SCV000675927.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
The p.S117* pathogenic mutation (also known as c.350C>A), located in coding exon 3 of the APC gene, results from a C to A substitution at … (more)
The p.S117* pathogenic mutation (also known as c.350C>A), located in coding exon 3 of the APC gene, results from a C to A substitution at nucleotide position 350. This changes the amino acid from a serine to a stop codon within coding exon 3. This mutation has been detected in multiple individuals with familial adenomatous polyposis (FAP) (Wu G et al. Genet. Test., 2001;5:281-90; Kerr SE et al. J Mol Diagn, 2013 Jan;15:31-43; Gutierrez Sanchez LH et al. Gastrointest Endosc, 2018 Mar;87:648-656.e3). In addition to the clinical data presented in the literature, 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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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
HelpTitle | Author | Journal | Year | Link |
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Hearing Status of Children and Adolescents With Familial Adenomatous Polyposis. | Findlen UM | Anticancer research | 2021 | PMID: 33788735 |
Upper GI involvement in children with familial adenomatous polyposis syndrome: single-center experience and meta-analysis of the literature. | Gutierrez Sanchez LH | Gastrointestinal endoscopy | 2018 | PMID: 29122597 |
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
APC germline mutations in individuals being evaluated for familial adenomatous polyposis: a review of the Mayo Clinic experience with 1591 consecutive tests. | Kerr SE | The Journal of molecular diagnostics : JMD | 2013 | PMID: 23159591 |
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 |
Detection of sequence variations in the adenomatous polyposis coli (APC) gene using denaturing high-performance liquid chromatography. | Wu G | Genetic testing | 2001 | PMID: 11960572 |
Text-mined citations for rs1064793535 ...
HelpRecord last updated Jul 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.