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NM_000038.6(APC):c.4732T>G (p.Cys1578Gly)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(3);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Jan 7, 2021)
Last evaluated:
Sep 21, 2020
Accession:
VCV000140839.12
Variation ID:
140839
Description:
single nucleotide variant
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NM_000038.6(APC):c.4732T>G (p.Cys1578Gly)

Allele ID
150553
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
5q22.2
Genomic location
5: 112840326 (GRCh38) GRCh38 UCSC
5: 112176023 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_130:g.152806T>G
NC_000005.10:g.112840326T>G
NC_000005.9:g.112176023T>G
... more HGVS
Protein change
C1560G, C1578G, C1553G, C1477G, C1487G, C1519G, C1418G, C1537G, C1550G, C1588G, C1596G, C1295G, C1452G
Other names
-
Canonical SPDI
NC_000005.10:112840325:T:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00000
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Links
ClinGen: CA009712
dbSNP: rs138367627
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Oct 21, 2019 RCV000507260.5
Likely pathogenic 1 criteria provided, single submitter Jul 29, 2020 RCV000129037.6
Likely pathogenic 1 criteria provided, single submitter Sep 21, 2020 RCV000206222.8
Likely pathogenic 1 criteria provided, single submitter Sep 25, 2018 RCV000236515.2
Uncertain significance 1 no assertion criteria provided Jun 1, 2014 RCV000148367.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
APC Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
9017 9051

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Jul 29, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000172947.7
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (5)
Comment:
The p.C1578G variant (also known as c.4732T>G), located in coding exon 15 of the APC gene, results from a T to G substitution at nucleotide … (more)
Likely pathogenic
(Sep 21, 2020)
criteria provided, single submitter
Method: clinical testing
Familial adenomatous polyposis 1
Allele origin: germline
Invitae
Accession: SCV000260260.9
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces cysteine with glycine at codon 1578 of the APC protein (p.Cys1578Gly). The cysteine residue is highly conserved and there is a … (more)
Likely pathogenic
(Sep 25, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000293423.11
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted APC c.4732T>G at the cDNA level, p.Cys1578Gly (C1578G) at the protein level, and results in the change of a Cysteine to … (more)
Uncertain significance
(May 18, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602503.2
Submitted: (Aug 05, 2019)
Evidence details
Comment:
The APC c.4732T>G; p.Cys1578Gly variant (rs138367627) is reported in the literature in an individual affected with multiple colorectal adenomas (Azzopardi 2008). This variant is found … (more)
Uncertain significance
(Oct 21, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918486.2
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (4)
Comment:
Variant summary: APC c.4732T>G (p.Cys1578Gly) results in a non-conservative amino acid change located in the SAMP repeats/axin binding domain (Azzopardi 2008) of the encoded protein … (more)
Uncertain significance
(Jun 01, 2014)
no assertion criteria provided
Method: research
Colorectal adenoma
(Autosomal dominant inheritance)
Allele origin: germline
CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190059.1
Submitted: (Aug 28, 2014)
Comment:
Variants classified for the Actionable exomic incidental findings in 6503 participants: challenges of variant classification manuscript
Evidence details

Functional evidence

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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 this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Amendola LM Genome research 2015 PMID: 25637381
Actionable, pathogenic incidental findings in 1,000 participants' exomes. Dorschner MO American journal of human genetics 2013 PMID: 24055113
Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer? Minde DP Molecular cancer 2011 PMID: 21859464
Multiple rare nonsynonymous variants in the adenomatous polyposis coli gene predispose to colorectal adenomas. Azzopardi D Cancer research 2008 PMID: 18199528
Structural basis of the Axin-adenomatous polyposis coli interaction. Spink KE The EMBO journal 2000 PMID: 10811618

Text-mined citations for rs138367627...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021