NM_000038.6(APC):c.3920T>A (p.Ile1307Lys) AND Familial adenomatous polyposis 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting interpretations of pathogenicity; risk factor (12 submissions)
Last evaluated:: Jul 7, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000020088.41

Allele description

NM_000038.6(APC):c.3920T>A (p.Ile1307Lys)

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.3920T>A (p.Ile1307Lys)

Other names:

p.I1307K:ATA>AAA; CCDS4107.1:c.3920T>A

HGVS:

NC_000005.10:g.112839514T>A
NG_008481.4:g.151994T>A
NM_000038.6:c.3920T>AMANE SELECT
NM_001127510.3:c.3920T>A
NM_001127511.3:c.3866T>A
NM_001354895.2:c.3920T>A
NM_001354896.2:c.3974T>A
NM_001354897.2:c.3950T>A
NM_001354898.2:c.3845T>A
NM_001354899.2:c.3836T>A
NM_001354900.2:c.3797T>A
NM_001354901.2:c.3743T>A
NM_001354902.2:c.3647T>A
NM_001354903.2:c.3617T>A
NM_001354904.2:c.3542T>A
NM_001354905.2:c.3440T>A
NM_001354906.2:c.3071T>A
NP_000029.2:p.Ile1307Lys
NP_001120982.1:p.Ile1307Lys
NP_001120983.2:p.Ile1289Lys
NP_001341824.1:p.Ile1307Lys
NP_001341825.1:p.Ile1325Lys
NP_001341826.1:p.Ile1317Lys
NP_001341827.1:p.Ile1282Lys
NP_001341828.1:p.Ile1279Lys
NP_001341829.1:p.Ile1266Lys
NP_001341830.1:p.Ile1248Lys
NP_001341831.1:p.Ile1216Lys
NP_001341832.1:p.Ile1206Lys
NP_001341833.1:p.Ile1181Lys
NP_001341834.1:p.Ile1147Lys
NP_001341835.1:p.Ile1024Lys
LRG_130t1:c.3920T>A
LRG_130:g.151994T>A
NC_000005.9:g.112175211T>A
NM_000038.3:c.3920T>A
NM_000038.4:c.3920T>A
NM_000038.5:c.3920T>A
NM_001127510.2:c.3920T>A
P25054:p.Ile1307Lys
p.I1307K

Nucleotide change:

3920T>A

Protein change:

I1024K; ILE1307LYS

Links:

UniProtKB: P25054#VAR_005049; OMIM: 611731.0029; dbSNP: rs1801155

NCBI 1000 Genomes Browser:

rs1801155

Molecular consequence:

NM_000038.6:c.3920T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.3920T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.3866T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.3920T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.3974T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.3950T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.3845T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.3836T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.3797T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.3743T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.3647T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.3617T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.3542T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.3440T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.3071T>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Familial adenomatous polyposis 1 (FAP1)
Synonyms:: POLYPOSIS, ADENOMATOUS INTESTINAL; FAMILIAL ADENOMATOUS POLYPOSIS 1, ATTENUATED; APC-Associated Polyposis Conditions
Identifiers:: MONDO: MONDO:0021056; MedGen: C2713442; OMIM: 175100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000040392	GeneReviews	no classification provided	not provided	unknown	literature only	PubMed (18) [See all records that cite these PMIDs] 10439961, 11001924, 11354631, 12173321, 12621137, 14624392, 9288102, 9585599, 9724771, 9731522, 9731533, 9751605, 9831355, 9869602, 9869603, 9869620, 9973276, 20301519
SCV000591159	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Uncertain significance	unknown	clinical testing
SCV000677724	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Likely pathogenic (Sep 27, 2016)	unknown	clinical testing	PubMed (13) [See all records that cite these PMIDs] 23576677, 24310308, 9288102, 23896379, 17854661, 24728327, 15712637, 9724771, 24599579, 24416237, 22703879, 11001924, 18343606 Citation Link,
SCV000838110	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely pathogenic (Jul 2, 2018)	unknown	clinical testing	Citation Link,
SCV000839876	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	risk factor (Jun 2, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000883121	Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 21, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001441544	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 3, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23576677, 23896379, 26421687, 9288102, 25741868
SCV001499607	Department of Molecular Diagnostics, Institute of Oncology Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 2, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001761068	New York Genome Center - CSER-NYCKidSeq	criteria provided, single submitter (NYGC Assertion Criteria 2020)	Established risk allele (May 26, 2023)	inherited, germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23896379, 23576677, 12173321 Citation Link,
SCV002030151	Baylor Genetics - CSER-TexasKidsCanSeq	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 27, 2021)	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003835790	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 15, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004015225	KCCC/NGS Laboratory, Kuwait Cancer Control Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 7, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	11	not provided	not provided	11	not provided	clinical testing
not provided	inherited	unknown	3	not provided	not provided	3	not provided	clinical testing
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Common origin of the I1307K APC polymorphism in Ashkenazi and non-Ashkenazi Jews.

Patael Y, Figer A, Gershoni-Baruch R, Papa MZ, Risel S, Shtoyerman-Chen R, Karasik A, Theodor L, Friedman E.

Eur J Hum Genet. 1999 Jul;7(5):555-9.

PubMed [citation]

PMID:: 10439961

Carrier rate of APC I1307K is not increased in inflammatory bowel disease patients of Ashkenazi Jewish origin.

Silverberg MS, Clelland C, Murphy JE, Steinhart AH, McLeod RS, Greenberg GR, Cohen Z, Siminovitch KA.

Hum Genet. 2001 Mar;108(3):205-10.

PubMed [citation]

PMID:: 11354631

See all PubMed Citations (30)

Details of each submission

From GeneReviews, SCV000040392.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (18)

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

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000591159.3

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

Description

The APC c.3920T>A (p.Ile1307Lys) variant was identified in 6 of 812 proband chromosomes (frequency: 0.007) from individuals or families with colorectal cancer and was present in 16 of 286 control chromosomes (frequency: 0.056) from healthy individuals (Fraying 1998, Nielsen 2005, Yantiss 2009). The p.Ile1307Lys variant was also identified in dbSNP (ID: rs1801155) as “With Pathogenic allele”; in NHLBI Exome Sequencing Project (Exome Variant Server), the variant was identified in 14 of 8600 European American alleles and was not found in 4404 African American alleles. In the Exome Aggregation Consortium database, the variant was identified 205 of 121054 chromosomes (frequency: 0.002), including 177 of 66620 alleles of European (Non-Finnish), 15 of 16502 of South Asian, 10 of 11546 of Latinos and 3 of 906 of Other alleles. The variant was not found in African, East Asian and Finnish populations. In the ClinVar database, the variant was identified by 8 submitters with conflicting classifications: classified as pathogenic by GeneReviews and by Ambry Genetics, (who used as assertion method the Ambry Genetics Dominant and X-linked criteria); GeneDx, Invitae, OMIM (2X) classified the variant as Risk Factor; Biesecker Laboratory ClinSeq Project-NHGRI classified the variant as Uncertain significance and ITMI did not provide a classification. The variant was identified in the UMD Colon cancer database and was classified as Neutral; in COSMIC it was identified in an adenocarcinoma tumour of the large intestine. In the InSIGHT database, the variant was identified 10X and classified as a low penetrance risk allele. The p.Ile1307 residue is not conserved in mammals and mouse has a valine at the 1307 position and fish and fruit fly carry the variant 1307Lys amino acid at this position, increasing the likelihood that this variant is benign. Computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant protein remains perfectly functional, yet the genetic alteration results in a small hypermutable region of DNA that may be prone to somatic mutations (Laken 1997). Several studies suggest that this variant increases risk of colon cancer. Woodage (1998) genotyped 5,081 Ashkenazi volunteers in a community survey, identifying 376 heterozygotes and 2 homozygotes (6.1%) and concluded that APC I1307K carriers have a modestly elevated risk of developing cancer (less than 2-fold). Woodage also emphasized that the large majority of I1307K carriers would not develop cancer of the colon. In addition, Gryfe (1999) identified the APC I1307K allele in 48 (10.1%) of 476 Ashkenazi Jewish subjects with adenomatous polyps and/or colorectal cancer. Compared with the frequency of 2 separate population control groups, the APC I1307K allele was associated with an estimated relative risk of 1.5 to 1.7 for colorectal neoplasia (P = 0.01). Compared with non-carriers, APC I1307K carriers had increased numbers of adenomas and colorectal cancers per patient, as well as a younger age at diagnosis. Fraying (1998), identified this variant in 3 individuals with multiple colonic adenomas, but also identified this variant in 8% of Ashkenazi controls from North London. In the most recent study (Boursi 2013), the variant was analyzed in 3305 Israelis undergoing colonoscopy; clinical data regarding potential risk factors were collected to determine if the p.Ile1307Lys variant was a risk factor in CRC in Ashkenazi Jews. This analysis included the prospective evaluation of 3305 consecutive Israeli subjects. Analysis consisted of high risk and average risk subjects. High risk (n=560) were diagnosed less than 60 years with family or personal history of CRC; Average risk (n=1779) were asymptomatic. It focused on a unique subpopulation of Ashkenazi Jews at average risk for CRC in order to assess the need to modify colonoscopy surveillance among p.I1307K carriers. Overall, the odds ratio for CRC among carriers was 1.51. Among average risk AJ patients the OR was 1.75 (adjusted for other risk factors). A recent meta-analysis of APC polymorphism and colorectal cancer from published data using pooled odds ratios and 95% confidence intervals were calculated by using Comprehensive Meta-Analysis software with a 2-tailed a-value of 0.05. Compared with those who carried the wild-type I1307K, Ashkenazi Jews who carried the I1307K variant were at a significantly increased risk for colorectal neoplasia, with a pooled odds ratio of 2.17 (95% confidence interval: 1.64-2.86)(Liang 2013). The authors suggest that the APC p.I1307K variant is an important risk factor for colorectal neoplasia in Ashkenazi Jews and carriers in this group should be considered for screening colonoscopy at the age of 40, to be repeated every 5 years, similar to recommendations in individuals with family history of colorectal cancer. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time, although this variant may be a low-penetrance allele that mildly increases the risk of developing colorectal cancer, it is not directly linked to a “polyposis” phenotype. Based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance in association with FAP. However, this variant is considered a risk factor for colorectal cancer.

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

From Counsyl, SCV000677724.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (13)

Description

I1307K is associated with a 10-20% lifetime risk of developing colon cancer in individuals of Ashkenazi Jewish ancestry and is not known to cause classic or attenuated FAP.

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

From Mendelics, SCV000838110.3

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

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

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV000839876.1

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

Description

The c.3920T>A (p.Ile1307Lys) variant in the APC gene has been reported as a common risk allele associated with familial colorectal cancer in the Ashkenazi Jewish population [PMID 18770064, 24416237]. The c.3920T>A variant has been reported to result in an adenine replacing a thymine and creating an oligo-adenine (A8) tract that appears to be inherently prone to further somatic mis-pairing and slippage during DNA replication, thereby creating a frameshift change [PMID 9288102, 18770064 and 244162370]. However, this variant has also been reported at a high frequency, present in 6% of Ashkenazi Jews and about 28% of Ashkenazim with a family history of colorectal cancer [PMID: 9288102]. Isoleucine at amino acid position 1307 of the APC protein is weakly conserved during evolution. While not validated for clinical use, the SIFT and PolyPhen-2 algorithms predict this variant to be benign. Ashkenazi Jews who carry the p.Ile1307Lys variant are at increased risk for colorectal neoplasia: the risk for colorectal neoplasia in heterozygous Ashkenazi Jewish individuals was estimated to be between 1.7 to 2.17 compared to non carrier individuals [PMID 12173321, 23576677, 23896379]. This variant is classified as as a risk allele with an increased risk for colorectal neoplasia in the Ashkenazi Jewish population. However the risk in non Jewish populations has not been determined.

#	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

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne, SCV000883121.1

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

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

From Johns Hopkins Genomics, Johns Hopkins University, SCV001441544.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

#	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

From Department of Molecular Diagnostics, Institute of Oncology Ljubljana, SCV001499607.1

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

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

From New York Genome Center - CSER-NYCKidSeq, SCV001761068.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)
2	not provided	1	not provided	not provided	clinical testing	PubMed (3)
3	not provided	1	not provided	not provided	clinical testing	PubMed (3)
4	not provided	1	not provided	not provided	clinical testing	PubMed (3)
5	not provided	1	not provided	not provided	clinical testing	PubMed (3)
6	not provided	1	not provided	not provided	clinical testing	PubMed (3)
7	not provided	1	not provided	not provided	clinical testing	PubMed (3)
8	not provided	1	not provided	not provided	clinical testing	PubMed (3)
9	not provided	1	not provided	not provided	clinical testing	PubMed (3)
10	not provided	1	not provided	not provided	clinical testing	PubMed (3)
11	not provided	1	not provided	not provided	clinical testing	PubMed (3)
12	not provided	1	not provided	not provided	clinical testing	PubMed (3)
13	not provided	1	not provided	not provided	clinical testing	PubMed (3)
14	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

The c.3920T>A p.(Ile1307Lys) variant identified in APC is a common variant with ~3.5% minor allele frequency in individuals of Ashkenazi Jewish ancestry (gnomAD v2.1 and v3.1.2). The variant affects a conserved residue located in beta-catening binding domain and changes the (A)3(T)(A)4 sequence element into an extended tract of adenosine nucleotides (A8) which might predispose to slippage of polymerase during DNA replication and confer increased propensity for somatic truncating mutations on the allele [PMID: 37076288]. It has been reported that individuals of Ashkenazi Jewish ancestry who carry the p.(Ile1307Lys) variant are 1.7-2.17 times more likely to develop colorectal neoplasia compared to non-carrier individuals [PMID: 23896379, 23576677, 12173321], hence this variant is classified as a risk allele for colorectal neoplasia in the Ashkenazi Jewish population.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	unknown	1	not provided	not provided		1	not provided	not provided	not provided
2	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided
3	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided
4	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided
5	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided
6	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided
7	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided
8	inherited	unknown	1	not provided	not provided		1	not provided	not provided	not provided
9	inherited	unknown	1	not provided	not provided		1	not provided	not provided	not provided
10	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided
11	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided
12	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided
13	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided
14	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided

From Baylor Genetics - CSER-TexasKidsCanSeq, SCV002030151.1

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

Description

This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

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

From Baylor Genetics, SCV003835790.1

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

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

From KCCC/NGS Laboratory, Kuwait Cancer Control Center, SCV004015225.1

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

Description

This sequence change replaces Isoleucine with Lysine at codon 1307 of the APC protein. The isoleucine residue is mildly conserved among species and is located in a known functional domain of the protein. There is a big physiochemical difference between isoleucine and lysine (Grantham Score 102). This variant is listed in population databases (rs1801155, ExAC 0.3) and is a common finding in individuals of Ashkenazi (~6-10%) and Sephardic Jewish decent (~3%; PMID: 9288102, 23896379). APC c.3920T>A (p.Ile1307Lys, also known as I1307K) has been associated with colorectal cancer. This variant has been observed in multiple ethnic backgrounds with highest frequencies in individuals of Ashkenazi Jewish ancestry and is present in ClinVar (ID: 822). Several large studies have showed increased risk for developing colorectal cancer in Ashkenazi Jewish population. However, the cancer risk remains unknown in individuals of non-Jewish descent. In summary, this variant is an established risk factor for colorectal cancer in Ashkenazi Jewish populations and variant of uncertain significance in other populations.

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

Last Updated: Jun 2, 2024

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