NM_000038.6(APC):c.4076A>G (p.Lys1359Arg) AND Familial adenomatous polyposis 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 19, 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:: RCV003653384.1

Allele description [Variation Report for NM_000038.6(APC):c.4076A>G (p.Lys1359Arg)]

NM_000038.6(APC):c.4076A>G (p.Lys1359Arg)

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.4076A>G (p.Lys1359Arg)

HGVS:

NC_000005.10:g.112839670A>G
NG_008481.4:g.152150A>G
NM_000038.6:c.4076A>GMANE SELECT
NM_001127510.3:c.4076A>G
NM_001127511.3:c.4022A>G
NM_001354895.2:c.4076A>G
NM_001354896.2:c.4130A>G
NM_001354897.2:c.4106A>G
NM_001354898.2:c.4001A>G
NM_001354899.2:c.3992A>G
NM_001354900.2:c.3953A>G
NM_001354901.2:c.3899A>G
NM_001354902.2:c.3803A>G
NM_001354903.2:c.3773A>G
NM_001354904.2:c.3698A>G
NM_001354905.2:c.3596A>G
NM_001354906.2:c.3227A>G
NP_000029.2:p.Lys1359Arg
NP_001120982.1:p.Lys1359Arg
NP_001120983.2:p.Lys1341Arg
NP_001341824.1:p.Lys1359Arg
NP_001341825.1:p.Lys1377Arg
NP_001341826.1:p.Lys1369Arg
NP_001341827.1:p.Lys1334Arg
NP_001341828.1:p.Lys1331Arg
NP_001341829.1:p.Lys1318Arg
NP_001341830.1:p.Lys1300Arg
NP_001341831.1:p.Lys1268Arg
NP_001341832.1:p.Lys1258Arg
NP_001341833.1:p.Lys1233Arg
NP_001341834.1:p.Lys1199Arg
NP_001341835.1:p.Lys1076Arg
LRG_130:g.152150A>G
NC_000005.9:g.112175367A>G
NM_000038.5:c.4076A>G

Protein change:

K1076R

Links:

dbSNP: rs1580643743

NCBI 1000 Genomes Browser:

rs1580643743

Molecular consequence:

NM_000038.6:c.4076A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.4076A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.4022A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.4076A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.4130A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.4106A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.4001A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.3992A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.3953A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.3899A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.3803A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.3773A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.3698A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.3596A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.3227A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000954841	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 19, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000954841

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 19, 2022)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000954841.4

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 657751). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1359 of the APC protein (p.Lys1359Arg).

#	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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Relating variation to medicine