NM_000038.6(APC):c.4349G>A (p.Arg1450Gln) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 13, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002265621.8

Allele description [Variation Report for NM_000038.6(APC):c.4349G>A (p.Arg1450Gln)]

NM_000038.6(APC):c.4349G>A (p.Arg1450Gln)

Gene:

APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.4349G>A (p.Arg1450Gln)

HGVS:

NC_000005.10:g.112839943G>A
NG_008481.4:g.152423G>A
NM_000038.6:c.4349G>AMANE SELECT
NM_001127510.3:c.4349G>A
NM_001127511.3:c.4295G>A
NM_001354895.2:c.4349G>A
NM_001354896.2:c.4403G>A
NM_001354897.2:c.4379G>A
NM_001354898.2:c.4274G>A
NM_001354899.2:c.4265G>A
NM_001354900.2:c.4226G>A
NM_001354901.2:c.4172G>A
NM_001354902.2:c.4076G>A
NM_001354903.2:c.4046G>A
NM_001354904.2:c.3971G>A
NM_001354905.2:c.3869G>A
NM_001354906.2:c.3500G>A
NP_000029.2:p.Arg1450Gln
NP_001120982.1:p.Arg1450Gln
NP_001120983.2:p.Arg1432Gln
NP_001341824.1:p.Arg1450Gln
NP_001341825.1:p.Arg1468Gln
NP_001341826.1:p.Arg1460Gln
NP_001341827.1:p.Arg1425Gln
NP_001341828.1:p.Arg1422Gln
NP_001341829.1:p.Arg1409Gln
NP_001341830.1:p.Arg1391Gln
NP_001341831.1:p.Arg1359Gln
NP_001341832.1:p.Arg1349Gln
NP_001341833.1:p.Arg1324Gln
NP_001341834.1:p.Arg1290Gln
NP_001341835.1:p.Arg1167Gln
LRG_130:g.152423G>A
NC_000005.9:g.112175640G>A
NM_000038.5:c.4349G>A
p.R1450Q

Protein change:

R1167Q

Links:

dbSNP: rs587782678

NCBI 1000 Genomes Browser:

rs587782678

Molecular consequence:

NM_000038.6:c.4349G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.4349G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.4295G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.4349G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.4403G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.4379G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.4274G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.4265G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.4226G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.4172G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.4076G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.4046G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.3971G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.3869G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.3500G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000694051	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (May 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27302369, 28859360 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000694051

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(May 13, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC.

Schell MJ, Yang M, Teer JK, Lo FY, Madan A, Coppola D, Monteiro AN, Nebozhyn MV, Yue B, Loboda A, Bien-Willner GA, Greenawalt DM, Yeatman TJ.

Nat Commun. 2016 Jun 15;7:11743. doi: 10.1038/ncomms11743.

PubMed [citation]

PMID:: 27302369
PMCID:: PMC4912618

Targeted next-generation sequencing of commonly mutated genes in esophageal adenocarcinoma patients with long-term survival.

Visser E, Franken IA, Brosens LAA, de Leng WWJ, Strengman E, Offerhaus JA, Ruurda JP, van Hillegersberg R.

Dis Esophagus. 2017 Sep 1;30(9):1-8. doi: 10.1093/dote/dox058.

PubMed [citation]

PMID:: 28859360

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000694051.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: APC c.4349G>A (p.Arg1450Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251192 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4349G>A has been reported in the literature in individuals affected with colorectal cancer and esophageal cancer (Schell_2016, Visser_2017) without strong evidence for causality. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Three laboratories classified the variant as uncertain significance and one as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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