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NM_000038.6(APC):c.4913T>C (p.Met1638Thr)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(4)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Mar 28, 2019)
Last evaluated:
Oct 13, 2018
Accession:
VCV000231898.3
Variation ID:
231898
Description:
single nucleotide variant
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NM_000038.6(APC):c.4913T>C (p.Met1638Thr)

Allele ID
233121
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
5q22.2
Genomic location
5: 112840507 (GRCh38) GRCh38 UCSC
5: 112176204 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000005.10:g.112840507T>C
NC_000005.9:g.112176204T>C
NM_000038.6:c.4913T>C NP_000029.2:p.Met1638Thr missense
... more HGVS
Protein change
M1620T
Other names
-
Functional consequence
-
Global minor allele frequency (GMAF)
0.00040 (C)

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00001
1000 Genomes Project 0.00040
The Genome Aggregation Database (gnomAD), exomes 0.00002
Links
ClinGen: CA040178
dbSNP: rs201797422
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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 Aug 18, 2018 RCV000213972.3
Likely benign 1 criteria provided, single submitter Jun 14, 2016 RCV000348692.1
Uncertain significance 1 criteria provided, single submitter Oct 13, 2018 RCV000549046.3
Uncertain significance 1 criteria provided, single submitter May 15, 2017 RCV000586239.1
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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
6125 6156

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Jun 14, 2016)
criteria provided, single submitter
Method: clinical testing
APC-Associated Polyposis Disorders
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000452018.2
Submitted: (Oct 18, 2016)
Evidence details
Uncertain significance
(May 15, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Integrated Genetics/Laboratory Corporation of America
Accession: SCV000694063.1
Submitted: (Jan 25, 2018)
Evidence details
Comment:
Variant summary: The APC c.4913T>C (p.Met1638Thr) variant involves the alteration of a conserved nucleotide located in the Adenomatous polyposis coli protein repeat region (InterPro). 2/4 ... (more)
Uncertain significance
(May 12, 2015)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000275885.4
Submitted: (Jul 30, 2018)
Evidence details
Comment:
Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Uncertain significance
(Aug 18, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color
Accession: SCV000681695.2
Submitted: (Nov 06, 2018)
Evidence details
Uncertain significance
(Oct 13, 2018)
criteria provided, single submitter
Method: clinical testing
Familial adenomatous polyposis 1
Allele origin: germline
Invitae
Accession: SCV000647546.3
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces methionine with threonine at codon 1638 of the APC protein (p.Met1638Thr). The methionine residue is moderately conserved and there is a ... (more)

Citations for this variant

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

Record last updated Jan 09, 2020