NM_000038.6(APC):c.3404A>G (p.Tyr1135Cys) AND Familial multiple polyposis syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 18, 2025
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:: RCV005240229.1

Allele description [Variation Report for NM_000038.6(APC):c.3404A>G (p.Tyr1135Cys)]

NM_000038.6(APC):c.3404A>G (p.Tyr1135Cys)

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.3404A>G (p.Tyr1135Cys)

HGVS:

NC_000005.10:g.112838998A>G
NG_008481.4:g.151478A>G
NM_000038.6:c.3404A>GMANE SELECT
NM_001127510.3:c.3404A>G
NM_001127511.3:c.3350A>G
NM_001354895.2:c.3404A>G
NM_001354896.2:c.3458A>G
NM_001354897.2:c.3434A>G
NM_001354898.2:c.3329A>G
NM_001354899.2:c.3320A>G
NM_001354900.2:c.3281A>G
NM_001354901.2:c.3227A>G
NM_001354902.2:c.3131A>G
NM_001354903.2:c.3101A>G
NM_001354904.2:c.3026A>G
NM_001354905.2:c.2924A>G
NM_001354906.2:c.2555A>G
NP_000029.2:p.Tyr1135Cys
NP_001120982.1:p.Tyr1135Cys
NP_001120983.2:p.Tyr1117Cys
NP_001341824.1:p.Tyr1135Cys
NP_001341825.1:p.Tyr1153Cys
NP_001341826.1:p.Tyr1145Cys
NP_001341827.1:p.Tyr1110Cys
NP_001341828.1:p.Tyr1107Cys
NP_001341829.1:p.Tyr1094Cys
NP_001341830.1:p.Tyr1076Cys
NP_001341831.1:p.Tyr1044Cys
NP_001341832.1:p.Tyr1034Cys
NP_001341833.1:p.Tyr1009Cys
NP_001341834.1:p.Tyr975Cys
NP_001341835.1:p.Tyr852Cys
LRG_130:g.151478A>G
NC_000005.9:g.112174695A>G
NM_000038.5:c.3404A>G

Protein change:

Y1009C

Links:

dbSNP: rs754916822

NCBI 1000 Genomes Browser:

rs754916822

Molecular consequence:

NM_000038.6:c.3404A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.3404A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.3350A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.3404A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.3458A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.3434A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.3329A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.3320A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.3281A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.3227A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.3131A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.3101A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.3026A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.2924A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.2555A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial multiple polyposis syndrome (FAP)
Synonyms:: Familial intestinal polyposis; Familial polyposis; Classic familial adenomatous polyposis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0021055; MedGen: C0032580; OMIM: PS175100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005885974	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Feb 18, 2025)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005885974

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Feb 18, 2025)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Role of next generation sequencing-based liquid biopsy in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: impact of STK11, KRAS and TP53 mutations and co-mutations on outcome.

Pavan A, Bragadin AB, Calvetti L, Ferro A, Zulato E, Attili I, Nardo G, Dal Maso A, Frega S, Menin AG, Fassan M, Calabrese F, Pasello G, Guarneri V, Aprile G, Conte P, Rosell R, Indraccolo S, Bonanno L.

Transl Lung Cancer Res. 2021 Jan;10(1):202-220. doi: 10.21037/tlcr-20-674.

PubMed [citation]

PMID:: 33569305
PMCID:: PMC7867770

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005885974.1

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

Description

Variant summary: APC c.3404A>G (p.Tyr1135Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250872 control chromosomes. c.3404A>G has been reported in the heterozygous state as a de novo variant (maternity and paternity confirmed) internally in at least 1 individual affected with clinical features of APC-related hereditary cancer (example, Labcorp Genetics (formerly Invitae)). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 490262). Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	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 16, 2025

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Relating variation to medicine