Variant summary: APC c.1477_1478dupTA (p.Ser494ThrfsX5) 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 251250 control chromosomes. To our knowledge, no occurrence of c.1477_1478dupTA in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.1477_1478dup (p.Ser494fs)
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_000038.6(APC):c.1477_1478dup (p.Ser494fs)
Variation ID: 1804874 Accession: VCV001804874.1
- Type and length
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Duplication, 2 bp
- Location
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Cytogenetic: 5q22.2 5: 112827175-112827176 (GRCh38) [ NCBI UCSC ] 5: 112162872-112162873 (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 24, 2022 Dec 24, 2022 Nov 3, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000038.6:c.1477_1478dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Ser494fs frameshift NM_001127510.3:c.1477_1478dup NP_001120982.1:p.Ser494fs frameshift NM_001127511.3:c.1423_1424dup NP_001120983.2:p.Ser476fs frameshift NM_001354895.2:c.1477_1478dup NP_001341824.1:p.Ser494fs frameshift NM_001354896.2:c.1531_1532dup NP_001341825.1:p.Ser512fs frameshift NM_001354897.2:c.1507_1508dup NP_001341826.1:p.Ser504fs frameshift NM_001354898.2:c.1402_1403dup NP_001341827.1:p.Ser469fs frameshift NM_001354899.2:c.1393_1394dup NP_001341828.1:p.Ser466fs frameshift NM_001354900.2:c.1354_1355dup NP_001341829.1:p.Ser453fs frameshift NM_001354901.2:c.1300_1301dup NP_001341830.1:p.Ser435fs frameshift NM_001354902.2:c.1204_1205dup NP_001341831.1:p.Ser403fs frameshift NM_001354903.2:c.1174_1175dup NP_001341832.1:p.Ser393fs frameshift NM_001354904.2:c.1099_1100dup NP_001341833.1:p.Ser368fs frameshift NM_001354905.2:c.997_998dup NP_001341834.1:p.Ser334fs frameshift NM_001354906.2:c.628_629dup NP_001341835.1:p.Ser211fs frameshift NM_001407446.1:c.1561_1562dup NP_001394375.1:p.Ser522Thrfs frameshift NM_001407447.1:c.1531_1532dup NP_001394376.1:p.Ser512Thrfs frameshift NM_001407448.1:c.1531_1532dup NP_001394377.1:p.Ser512Thrfs frameshift NM_001407449.1:c.1531_1532dup NP_001394378.1:p.Ser512Thrfs frameshift NM_001407450.1:c.1477_1478dup NP_001394379.1:p.Ser494Thrfs frameshift NM_001407451.1:c.1456_1457dup NP_001394380.1:p.Ser487Thrfs frameshift NM_001407452.1:c.1447_1448dup NP_001394381.1:p.Ser484Thrfs frameshift NM_001407453.1:c.1300_1301dup NP_001394382.1:p.Ser435Thrfs frameshift NM_001407454.1:c.1228_1229dup NP_001394383.1:p.Ser411Thrfs frameshift NM_001407455.1:c.1228_1229dup NP_001394384.1:p.Ser411Thrfs frameshift NM_001407456.1:c.1228_1229dup NP_001394385.1:p.Ser411Thrfs frameshift NM_001407457.1:c.1228_1229dup NP_001394386.1:p.Ser411Thrfs frameshift NM_001407458.1:c.1174_1175dup NP_001394387.1:p.Ser393Thrfs frameshift NM_001407459.1:c.1174_1175dup NP_001394388.1:p.Ser393Thrfs frameshift NM_001407460.1:c.1174_1175dup NP_001394389.1:p.Ser393Thrfs frameshift NM_001407467.1:c.1090_1091dup NP_001394396.1:p.Ser365Thrfs frameshift NM_001407469.1:c.1090_1091dup NP_001394398.1:p.Ser365Thrfs frameshift NM_001407470.1:c.628_629dup NP_001394399.1:p.Ser211Thrfs frameshift NM_001407471.1:c.325_326dup NP_001394400.1:p.Ser110Thrfs frameshift NM_001407472.1:c.325_326dup NP_001394401.1:p.Ser110Thrfs frameshift NC_000005.10:g.112827176_112827177dup NC_000005.9:g.112162873_112162874dup NG_008481.4:g.139656_139657dup LRG_130:g.139656_139657dup LRG_130t1:c.1477_1478dup LRG_130p1:p.Ser494Thrfs LRG_130t2:c.1477_1478dup LRG_130p2:p.Ser494Thrfs LRG_130t3:c.1477_1478dup LRG_130p3:p.Ser494Thrfs - Protein change
- S494fs, S504fs, S512fs, S211fs, S334fs, S368fs, S393fs, S403fs, S435fs, S453fs, S466fs, S469fs, S476fs
- Other names
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- Canonical SPDI
- NC_000005.10:112827175:TA:TATA
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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 |
14965 | 15103 | |
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. |
|---|---|---|---|---|
| Likely pathogenic (1) |
criteria provided, single submitter
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Nov 3, 2022 | RCV002470171.1 |
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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Likely pathogenic
(Nov 03, 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: SCV002766584.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Variant summary: APC c.1477_1478dupTA (p.Ser494ThrfsX5) 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.1477_1478dupTA (p.Ser494ThrfsX5) 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 251250 control chromosomes. To our knowledge, no occurrence of c.1477_1478dupTA in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely 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:
Variant summary: APC c.1477_1478dupTA (p.Ser494ThrfsX5) 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 251250 control chromosomes. To our knowledge, no occurrence of c.1477_1478dupTA in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely 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 Jun 02, 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.