ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.3183_3187del (p.Lys1061_Gln1062insTer)
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.3183_3187del (p.Lys1061_Gln1062insTer)
Variation ID: 88913 Accession: VCV000088913.61
- Type and length
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Deletion, 5 bp
- Location
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Cytogenetic: 5q22.2 5: 112838774-112838778 (GRCh38) [ NCBI UCSC ] 5: 112174471-112174475 (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 Oct 19, 2014 May 1, 2024 Jan 30, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000038.6:c.3183_3187del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Lys1061_Gln1062insTer frameshift NM_000038.6:c.3183_3187delACAAA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001127510.3:c.3183_3187del NP_001120982.1:p.Lys1061_Gln1062insTer frameshift NM_001127511.3:c.3129_3133del NP_001120983.2:p.Lys1043_Gln1044insTer frameshift NM_001354895.2:c.3183_3187del NP_001341824.1:p.Lys1061_Gln1062insTer frameshift NM_001354896.2:c.3237_3241del NP_001341825.1:p.Lys1079_Gln1080insTer frameshift NM_001354897.2:c.3213_3217del NP_001341826.1:p.Lys1071_Gln1072insTer frameshift NM_001354898.2:c.3108_3112del NP_001341827.1:p.Lys1036_Gln1037insTer frameshift NM_001354899.2:c.3099_3103del NP_001341828.1:p.Lys1033_Gln1034insTer frameshift NM_001354900.2:c.3060_3064del NP_001341829.1:p.Lys1020_Gln1021insTer frameshift NM_001354901.2:c.3006_3010del NP_001341830.1:p.Lys1002_Gln1003insTer frameshift NM_001354902.2:c.2910_2914del NP_001341831.1:p.Lys970_Gln971insTer frameshift NM_001354903.2:c.2880_2884del NP_001341832.1:p.Lys960_Gln961insTer frameshift NM_001354904.2:c.2805_2809del NP_001341833.1:p.Lys935_Gln936insTer frameshift NM_001354905.2:c.2703_2707del NP_001341834.1:p.Lys901_Gln902insTer frameshift NM_001354906.2:c.2334_2338del NP_001341835.1:p.Lys778_Gln779insTer frameshift NM_001407446.1:c.3267_3271delACAAA NP_001394375.1:p.Gln1090Terfs frameshift nonsense NM_001407447.1:c.3237_3241delACAAA NP_001394376.1:p.Gln1080Terfs frameshift nonsense NM_001407448.1:c.3237_3241delACAAA NP_001394377.1:p.Gln1080Terfs frameshift nonsense NM_001407449.1:c.3237_3241delACAAA NP_001394378.1:p.Gln1080Terfs frameshift nonsense NM_001407450.1:c.3183_3187delACAAA NP_001394379.1:p.Gln1062Terfs frameshift nonsense NM_001407451.1:c.3162_3166delACAAA NP_001394380.1:p.Gln1055Terfs frameshift nonsense NM_001407452.1:c.3153_3157delACAAA NP_001394381.1:p.Gln1052Terfs frameshift nonsense NM_001407453.1:c.3006_3010delACAAA NP_001394382.1:p.Gln1003Terfs frameshift nonsense NM_001407454.1:c.2934_2938delACAAA NP_001394383.1:p.Gln979Terfs frameshift nonsense NM_001407455.1:c.2934_2938delACAAA NP_001394384.1:p.Gln979Terfs frameshift nonsense NM_001407456.1:c.2934_2938delACAAA NP_001394385.1:p.Gln979Terfs frameshift nonsense NM_001407457.1:c.2934_2938delACAAA NP_001394386.1:p.Gln979Terfs frameshift nonsense NM_001407458.1:c.2880_2884delACAAA NP_001394387.1:p.Gln961Terfs frameshift nonsense NM_001407459.1:c.2880_2884delACAAA NP_001394388.1:p.Gln961Terfs frameshift nonsense NM_001407460.1:c.2880_2884delACAAA NP_001394389.1:p.Gln961Terfs frameshift nonsense NM_001407467.1:c.2796_2800delACAAA NP_001394396.1:p.Gln933Terfs frameshift nonsense NM_001407469.1:c.2796_2800delACAAA NP_001394398.1:p.Gln933Terfs frameshift nonsense NM_001407470.1:c.2334_2338delACAAA NP_001394399.1:p.Gln779Terfs frameshift nonsense NM_001407471.1:c.2031_2035delACAAA NP_001394400.1:p.Gln678Terfs frameshift nonsense NM_001407472.1:c.2031_2035delACAAA NP_001394401.1:p.Gln678Terfs frameshift nonsense NR_176365.1:n.3018_3022delACAAA NR_176366.1:n.3437_3441delACAAA NC_000005.10:g.112838777_112838781del NC_000005.9:g.112174474_112174478del NG_008481.4:g.151257_151261del LRG_130:g.151257_151261del LRG_130t1:c.3183_3187del LRG_130p1:p.Gln1062Terfs LRG_130t2:c.3183_3187del LRG_130p2:p.Gln1062Terfs LRG_130t3:c.3183_3187del LRG_130p3:p.Gln1062Terfs - Protein change
- Other names
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- Canonical SPDI
- NC_000005.10:112838773:AAAACAAA:AAA
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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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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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APC | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
14091 | 14225 |
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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Pathogenic (12) |
criteria provided, multiple submitters, no conflicts
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Dec 1, 2023 | RCV000077987.48 | |
Pathogenic (9) |
criteria provided, multiple submitters, no conflicts
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Jul 7, 2023 | RCV000144562.26 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 31, 2022 | RCV000162768.17 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 28, 2019 | RCV000502016.12 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 29, 2016 | RCV000722012.9 | |
Pathogenic (1) |
no assertion criteria provided
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- | RCV001353466.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 30, 2024 | RCV003743559.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 15, 2023 | RCV003997058.1 |
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 28, 2018)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: yes
Allele origin:
germline
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National Molecular Genetics Centre of Cancer Research, N.N. Alexandrov National Cancer Centre of Belarus
Accession: SCV000778310.1
First in ClinVar: May 26, 2018 Last updated: May 26, 2018 |
Comment:
This sequence change (c.3183_3187delACAAA) creates a stop codon (p.Gln1062*) in exon 16 of the APC mRNA.
Clinical Features:
Adenomatous colonic polyposis (present)
Indication for testing: Clinical features observed in this individual
Age: 30-39 years
Sex: female
Ethnicity/Population group: Caucasian
Geographic origin: Republic of Belarus
Method: Bidirectional sequencing of the entire coding region of APC gene.
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Pathogenic
(Nov 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Familial multiple polyposis syndrome
Affected status: yes
Allele origin:
germline
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Center for Human Genetics, Inc, Center for Human Genetics, Inc
Accession: SCV000781075.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
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Pathogenic
(Aug 22, 2013)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000226392.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 30, 2019 |
Number of individuals with the variant: 5
Sex: mixed
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Pathogenic
(Jan 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: no
Allele origin:
germline
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GeneKor MSA
Accession: SCV000821693.2
First in ClinVar: Oct 10, 2018 Last updated: Apr 22, 2020 |
Comment:
This variation is a deletion of five nucleotides at position 1062 of the APC protein, resulting in the formation of new stop codon. Thus, a … (more)
This variation is a deletion of five nucleotides at position 1062 of the APC protein, resulting in the formation of new stop codon. Thus, a premature protein. This results in premature termination of protein synthesis and inactivation of one allele. This particular mutation has been described in international literature in patients with Familial adenomatous polyposis (PMID: 1316610, PMID: 8162022, PMID: 15771908). This mutation has been described in the mutation database ClinVar (Variation ID: 55683). (less)
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446775.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Sex: male
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Pathogenic
(May 06, 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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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001450058.1
First in ClinVar: Dec 10, 2020 Last updated: Dec 10, 2020 |
Number of individuals with the variant: 1
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Pathogenic
(Jul 29, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000256968.3
First in ClinVar: Nov 20, 2015 Last updated: Mar 12, 2021 |
Comment:
PVS1, PS4_Mod, PP4
Number of individuals with the variant: 3
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Pathogenic
(Jan 15, 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: SCV000905975.3
First in ClinVar: May 20, 2019 Last updated: Jan 12, 2022 |
Comment:
This variant deletes 5 nucleotides in exon 16 of the APC gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 5 nucleotides in exon 16 of the APC gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 1/250490 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of APC function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Jul 02, 2018)
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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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Mendelics
Accession: SCV000838100.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
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Pathogenic
(Mar 03, 2016)
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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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Counsyl
Accession: SCV000488338.2
First in ClinVar: Jul 01, 2016 Last updated: Dec 24, 2022 |
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Pathogenic
(Apr 13, 2022)
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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: SCV000293390.13
First in ClinVar: Jul 24, 2016 Last updated: Mar 04, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant … (more)
Nonsense variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 15024739, 1316610, 11106555, 20649969, 15951557, 8162051, 19029688, 20007843, 25248397, 28127413, 27143045, 30897307, 19531215, 31469036, 16088911, 11748858, 11933206, 9375853, 8381581, 10083733, 10363573, 12007223, 10646887, 9950360, 7833931, 8395941, 8730280, 8381579, 8544194, 8162022, 20223039, 8990002, 18433509, 14961559, 20333795, 26625971, 25832318, 28533537, 28331559, 28135145, 26840078, 28975465, 29351919, 22692730, 29753700, 31069152, 30720243, 31159747, 27000756, 26446593, 20924072, 16134147, 31504825, 31598872, 18629513) (less)
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Pathogenic
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: yes
Allele origin:
unknown
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004015214.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This sequence change results in a premature translational stop signal in the APC gene (p.Gln1062*). This variant has been observed in several individuals affected with … (more)
This sequence change results in a premature translational stop signal in the APC gene (p.Gln1062*). This variant has been observed in several individuals affected with familial adenomatous polyposis (PMID: 1316610, 8162022, 15771908). ClinVar contains an entry for this variant (Variation ID: 88913) with 21 submissions all of which describe this variant as pathogenic. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120). Therefore, this variant has been classified as pathogenic. (less)
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Pathogenic
(Feb 22, 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: SCV004018789.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 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
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004025049.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
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Pathogenic
(Jul 01, 2023)
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criteria provided, single submitter
Method: research
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Familial adenomatous polyposis 1
Affected status: yes
Allele origin:
germline
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Division of Human Genetics, National Health Laboratory Service/University of the Witwatersrand
Accession: SCV004034115.1
First in ClinVar: Sep 16, 2023 Last updated: Sep 16, 2023 |
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Pathogenic
(Jul 03, 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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Baylor Genetics
Accession: SCV004202210.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(May 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600078.3
First in ClinVar: Sep 28, 2017 Last updated: Jan 06, 2024 |
Comment:
The APC c.3183_3187del (p.Gln1062*) variant causes the premature termination of APC protein synthesis. This variant has been reported in the published literature in affected individuals … (more)
The APC c.3183_3187del (p.Gln1062*) variant causes the premature termination of APC protein synthesis. This variant has been reported in the published literature in affected individuals with familial adenomatous polyposis (FAP) (PMIDs: 1316610 (1992), 8381579 (1993), 23159591 (2013), 26446593 (2016), 26625971 (2016), and 35189564 (2022)), medulloblastoma (PMIDs: 29351919 (2018), 29753700 (2018), and 31504825 (2020)), papillary thyroid carcinoma (PMID: 31469036 (2019), and breast and/or ovarian cancer (PMID: 31159747 (2019)). This variant was also reported to segregate with disease and occurred as de novo in unrelated patients (PMID: 8381579 (1993)). The frequency of this variant in the general population, 0.0000089 (1/112982 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Dec 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003815521.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(May 01, 2022)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001500823.17
First in ClinVar: Mar 12, 2021 Last updated: Apr 15, 2024 |
Comment:
APC: PVS1:Strong, PM1, PM2, PS4:Moderate
Number of individuals with the variant: 2
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Pathogenic
(Feb 29, 2016)
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criteria provided, single submitter
Method: clinical testing
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Craniopharyngioma
Affected status: yes
Allele origin:
germline
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St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Accession: SCV000853185.1
First in ClinVar: Nov 25, 2018 Last updated: Nov 25, 2018 |
Comment:
This is a frameshift mutation in which 5 nucleotides are deleted between coding positions 3183 and 3187 and is predicted to shift the reading frame … (more)
This is a frameshift mutation in which 5 nucleotides are deleted between coding positions 3183 and 3187 and is predicted to shift the reading frame at codon 1061. (less)
Sex: female
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Pathogenic
(Oct 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694026.2
First in ClinVar: Feb 19, 2018 Last updated: Jun 22, 2020 |
Comment:
Variant summary: APC c.3183_3187delACAAA (p.Gln1062X) 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.3183_3187delACAAA (p.Gln1062X) 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. The variant allele was found at a frequency of 4e-06 in 250490 control chromosomes (gnomAD). c.3183_3187delACAAA has been reported in the literature in multiple individuals affected with Familial Adenomatous Polyposis and colorectal cancer (Inra_2015, Miyoshi_1992, Papp_2016). These data indicate that the variant is very likely to be associated with disease. 11 ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Apr 02, 2020)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: yes
Allele origin:
germline
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Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499606.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
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Pathogenic
(Jan 30, 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: SCV000253730.12
First in ClinVar: Oct 11, 2015 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln1062*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Gln1062*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1782 amino acid(s) of the APC protein. This variant is present in population databases (rs587779352, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 1316610, 8162022, 15771908). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 88913). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jun 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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Classic or attenuated familial adenomatous polyposis
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004839779.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This variant creates a premature termination codon in the last exon. The transcribed mRNA is predicted to escape nonsense mediated decay and result in protein … (more)
This variant creates a premature termination codon in the last exon. The transcribed mRNA is predicted to escape nonsense mediated decay and result in protein truncation. This prediction has not been confirmed by functional studies. This variant has been reported in multiple individuals with familial adenomatous polyposis (PMID: 9101302, 9375853, 9703421, 11677205, 23159591). This variant is absent from or rare in large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). (less)
Number of individuals with the variant: 1
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Pathogenic
(Mar 31, 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: SCV000213245.9
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The c.3183_3187delACAAA pathogenic mutation (also known as p.Q1062*), located in coding exon 15 of the APC gene, results from a deletion of 5 nucleotides at … (more)
The c.3183_3187delACAAA pathogenic mutation (also known as p.Q1062*), located in coding exon 15 of the APC gene, results from a deletion of 5 nucleotides at nucleotide positions 3183 to 3187. This changes the amino acid from a glutamine to a stop codon within coding exon 15. This mutation has been identified in numerous individuals and families from a variety of ethnic backgrounds with classic familial adenomatous polyposis (FAP), including some individuals with extra colonic manifestations including desmoid tumors, gastrointestinal cancers, papillary thyroid cancer, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and epidermal cysts (Miyoshi Y et al. Proc. Natl. Acad. Sci. U.S.A. 1992 May;89:4452-6; Won YJ et al. J. Hum. Genet. 1999;44:103-8; González S et al. Cancer Genet. Cytogenet. 2005 Apr;158:70-4; Kim DW et al. Hum. Mutat. 2005 Sep;26:281; Friedl W & Aretz S. Hered. Cancer Clin. Pract. 2005 Sep;3:95-114; Plawski A & Slomski R. J. Appl. Genet. 2008;49:407-14; Fostira F et al. BMC Cancer. 2010 Jul;10:389; Rivera B et al. Ann. Oncol. 2011 Apr;22:903-9; Kerr SE et al. J. Mol. Diagn. 2013 Jan;15:31-43; Papp J et al. Fam. Cancer. 2016 Jan;15(1):85-97; Dahl NA et al. J. Pediatr. Hematol. Oncol. 2016 07;38(5):e154-7). Of note, this alteration is also described as a truncation at codon 1061 or codon 1060, and as c.3221_3225delACAAA in the literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Jul 24, 2014)
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no assertion criteria provided
Method: clinical testing
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Adenomatous polyposis coli
Affected status: unknown
Allele origin:
germline
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Pathway Genomics
Accession: SCV000189853.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Carcinoma of colon
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591132.3 First in ClinVar: Aug 28, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Gln1062X variant has been described as a common hotspot mutation in the literature, with a founder effect in at least one population (from the … (more)
The p.Gln1062X variant has been described as a common hotspot mutation in the literature, with a founder effect in at least one population (from the Spanish Balearic Islands) (Fostira 2010, Gonzales 2005). In six studies it was identified in 36 of 4386 chromosomes (frequency: 0.008) from individuals or families with familial adenomatous polyposis or colorectal cancer (Aceto 2005, Fostira 2010, Gonzales 2005, Kerr 2012, Plawski 2008, Wallis 1999), and was absent in control chromosomes from these studies. The variant was also identified in several database searches, including: GeneInsight COGR (classified as pathogenic by a clinical laboratory), HGMD, UMD (208X as a “causal” variant), COSMIC, Clinvitae, InSiGHT Colon Cancer Database (191X), Zhejiang Colon Cancer Database, and the ClinVar Database (classified as pathogenic by Emory Genetics Laboratory, Pathway Genomics, and Ambry Genetics). The p.Gln1062X variant leads to a premature stop codon at position 1062, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the APC gene are an established mechanism of disease in familial adenomatous polyposis and is the type of variant expected to cause the disorder. Notably, this variant occurs in the last exon of the gene and stop codon or nonsense mutations in this region may not be subjected to nonsense mediated RNA decay, although further study would be required to validate this hypothesis and it is currently not possible to determine whether or not this might influence the severity of the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001744538.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001965512.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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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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Using genotype to assist clinical surveillance: a retrospective study of Chinese familial adenomatous polyposis patients. | Ge S | American journal of cancer research | 2022 | PMID: 36225625 |
Necessity of multiplex ligation probe amplification in genetic tests: Germline variant analysis of the APC gene in familial adenomatous polyposis patients. | Lee JK | Cancer genetics | 2022 | PMID: 35189564 |
Medulloblastomas associated with an APC germline pathogenic variant share the good prognosis of CTNNB1-mutated medulloblastomas. | Surun A | Neuro-oncology | 2020 | PMID: 31504825 |
Multifocality in a Patient with Cribriform-Morular Variant of Papillary Thyroid Carcinoma Is an Important Clue for the Diagnosis of Familial Adenomatous Polyposis. | Park J | Thyroid : official journal of the American Thyroid Association | 2019 | PMID: 31469036 |
Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations. | Tsaousis GN | BMC cancer | 2019 | PMID: 31159747 |
Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort. | Waszak SM | The Lancet. Oncology | 2018 | PMID: 29753700 |
High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer. | Diets IJ | Clinical cancer research : an official journal of the American Association for Cancer Research | 2018 | PMID: 29351919 |
Gardner Fibroma: Clinical and Histopathologic Implications of Germline APC Mutation Association. | Dahl NA | Journal of pediatric hematology/oncology | 2016 | PMID: 26840078 |
Novel and reported APC germline mutations in Chinese patients with familial adenomatous polyposis. | Zhang S | Gene | 2016 | PMID: 26625971 |
Contribution of APC and MUTYH mutations to familial adenomatous polyposis susceptibility in Hungary. | Papp J | Familial cancer | 2016 | PMID: 26446593 |
Attenuated familial adenomatous polyposis with desmoids caused by an APC mutation. | Ikenoue T | Human genome variation | 2015 | PMID: 27081525 |
Racial variation in frequency and phenotypes of APC and MUTYH mutations in 6,169 individuals undergoing genetic testing. | Inra JA | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25590978 |
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 |
Prevalence of skin lesions in familial adenomatous polyposis: a marker for presymptomatic diagnosis? | Burger B | The oncologist | 2011 | PMID: 22135120 |
Clinical and genetic characterization of classical forms of familial adenomatous polyposis: a Spanish population study. | Rivera B | Annals of oncology : official journal of the European Society for Medical Oncology | 2011 | PMID: 20924072 |
Mutational spectrum of APC and genotype-phenotype correlations in Greek FAP patients. | Fostira F | BMC cancer | 2010 | PMID: 20649969 |
APC gene mutations causing familial adenomatous polyposis in Polish patients. | Plawski A | Journal of applied genetics | 2008 | PMID: 19029688 |
One-hit effects in cancer: altered proteome of morphologically normal colon crypts in familial adenomatous polyposis. | Yeung AT | Cancer research | 2008 | PMID: 18794146 |
Regulated binding of adenomatous polyposis coli protein to actin. | Moseley JB | The Journal of biological chemistry | 2007 | PMID: 17293347 |
Mutation spectrum of the APC gene in 83 Korean FAP families. | Kim DW | Human mutation | 2005 | PMID: 16088911 |
Founder mutation in familial adenomatous polyposis (FAP) in the Balearic Islands. | González S | Cancer genetics and cytogenetics | 2005 | PMID: 15771908 |
EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. | Wen Y | Nature cell biology | 2004 | PMID: 15311282 |
Analysis of chromosomal instability in human colorectal adenomas with two mutational hits at APC. | Sieber OM | Proceedings of the National Academy of Sciences of the United States of America | 2002 | PMID: 12486240 |
Preliminary results of the molecular diagnosis of familial adenomatous polyposis in Cuban families. | Cruz-Bustillo D | International journal of colorectal disease | 2002 | PMID: 12172928 |
Periampullary adenomas and adenocarcinomas in familial adenomatous polyposis: cumulative risks and APC gene mutations. | Björk J | Gastroenterology | 2001 | PMID: 11677205 |
Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families. | Friedl W | Gut | 2001 | PMID: 11247896 |
Germline mutations of the APC gene in Korean familial adenomatous polyposis patients. | Won YJ | Journal of human genetics | 1999 | PMID: 10083733 |
Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene. | Brensinger JD | Gut | 1998 | PMID: 9824584 |
The familial adenomatous polyposis region exhibits many different haplotypes. | Stella A | Human genetics | 1998 | PMID: 9703421 |
APC mutations in familial adenomatous polyposis families in the Northwest of England. | Armstrong JG | Human mutation | 1997 | PMID: 9375853 |
Characterization of 19 novel and six recurring APC mutations in Italian adenomatous polyposis patients, using two different mutation detection techniques. | Gismondi V | Human mutation | 1997 | PMID: 9101302 |
Frequency of common and novel inactivating APC mutations in 202 families with familial adenomatous polyposis. | Mandl M | Human molecular genetics | 1994 | PMID: 8162022 |
Identical APC exon 15 mutations result in a variable phenotype in familial adenomatous polyposis. | Paul P | Human molecular genetics | 1993 | PMID: 8395941 |
Identification of APC gene mutations in Italian adenomatous polyposis coli patients by PCR-SSCP analysis. | Varesco L | American journal of human genetics | 1993 | PMID: 8381581 |
Mutational analysis of patients with adenomatous polyposis: identical inactivating mutations in unrelated individuals. | Groden J | American journal of human genetics | 1993 | PMID: 8381579 |
Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. | Miyoshi Y | Proceedings of the National Academy of Sciences of the United States of America | 1992 | PMID: 1316610 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=APC | - | - | - | - |
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Text-mined citations for rs587779352 ...
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.