NM_000038.6(APC):c.4778del (p.Lys1593fs) AND Familial adenomatous polyposis 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 26, 2023
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV003148798.3

Allele description [Variation Report for NM_000038.6(APC):c.4778del (p.Lys1593fs)]

NM_000038.6(APC):c.4778del (p.Lys1593fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.4778del (p.Lys1593fs)

Other names:

NM_000038.6(APC):c.4778del; p.Lys1593fs

HGVS:

NC_000005.10:g.112840372del
NG_008481.4:g.152852del
NM_000038.5:c.4778del
NM_000038.6:c.4778delMANE SELECT
NM_001127510.3:c.4778del
NM_001127511.3:c.4724del
NM_001354895.2:c.4778del
NM_001354896.2:c.4832del
NM_001354897.2:c.4808del
NM_001354898.2:c.4703del
NM_001354899.2:c.4694del
NM_001354900.2:c.4655del
NM_001354901.2:c.4601del
NM_001354902.2:c.4505del
NM_001354903.2:c.4475del
NM_001354904.2:c.4400del
NM_001354905.2:c.4298del
NM_001354906.2:c.3929del
NP_000029.2:p.Lys1593fs
NP_001120982.1:p.Lys1593fs
NP_001120983.2:p.Lys1575fs
NP_001341824.1:p.Lys1593fs
NP_001341825.1:p.Lys1611fs
NP_001341826.1:p.Lys1603fs
NP_001341827.1:p.Lys1568fs
NP_001341828.1:p.Lys1565fs
NP_001341829.1:p.Lys1552fs
NP_001341830.1:p.Lys1534fs
NP_001341831.1:p.Lys1502fs
NP_001341832.1:p.Lys1492fs
NP_001341833.1:p.Lys1467fs
NP_001341834.1:p.Lys1433fs
NP_001341835.1:p.Lys1310fs
LRG_130:g.152852del
NC_000005.9:g.112176069del
NM_000038.5:c.4778delA

Protein change:

K1310fs

Links:

dbSNP: rs1554086185

NCBI 1000 Genomes Browser:

rs1554086185

Molecular consequence:

NM_000038.6:c.4778del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127510.3:c.4778del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127511.3:c.4724del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354895.2:c.4778del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354896.2:c.4832del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354897.2:c.4808del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354898.2:c.4703del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354899.2:c.4694del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354900.2:c.4655del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354901.2:c.4601del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354902.2:c.4505del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354903.2:c.4475del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354904.2:c.4400del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354905.2:c.4298del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354906.2:c.3929del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV003836605	ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel	reviewed by expert panel (ClinGen InSiGHT HCCP VCEP ACMG Specifications APC V1)	Pathogenic (Feb 26, 2023)	germline	curation	Citation Link,
SCV004045076	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (May 11, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003836605

ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel

reviewed by expert panel

(ClinGen InSiGHT HCCP VCEP ACMG Specifications APC V1)

Pathogenic
(Feb 26, 2023)

germline

curation

Citation Link,

SCV004045076

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Pathogenic
(May 11, 2023)

unknown

clinical testing

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	curation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel, SCV003836605.1

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

Description

The c.4778del p.(Lys1593Serfs*57) variant in APC is a frameshift variant located between codon 49 and 2645 and predicted to cause a premature stop codon in exon 16 in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has been reported in 2 probands meeting phenotypic criteria, resulting in a total phenotype score of 1 (PS4_Supporting, Internal lab contributors). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant is classified as Pathogenic for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: PVS1, PS4_Supporting, PM2_Supporting (VCEP specifications version 1; date of approval: 12/12/2022).

#	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 Myriad Genetics, Inc., SCV004045076.2

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

Description

This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

#	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

Last Updated: May 16, 2025

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