NM_000038.6(APC):c.5431T>C (p.Ser1811Pro) AND Familial adenomatous polyposis 1

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 30, 2020
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:: RCV000700210.3

Allele description

NM_000038.6(APC):c.5431T>C (p.Ser1811Pro)

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.5431T>C (p.Ser1811Pro)

HGVS:

NC_000005.10:g.112841025T>C
NG_008481.4:g.153505T>C
NM_000038.6:c.5431T>CMANE SELECT
NM_001127510.3:c.5431T>C
NM_001127511.3:c.5377T>C
NM_001354895.2:c.5431T>C
NM_001354896.2:c.5485T>C
NM_001354897.2:c.5461T>C
NM_001354898.2:c.5356T>C
NM_001354899.2:c.5347T>C
NM_001354900.2:c.5308T>C
NM_001354901.2:c.5254T>C
NM_001354902.2:c.5158T>C
NM_001354903.2:c.5128T>C
NM_001354904.2:c.5053T>C
NM_001354905.2:c.4951T>C
NM_001354906.2:c.4582T>C
NP_000029.2:p.Ser1811Pro
NP_001120982.1:p.Ser1811Pro
NP_001120983.2:p.Ser1793Pro
NP_001341824.1:p.Ser1811Pro
NP_001341825.1:p.Ser1829Pro
NP_001341826.1:p.Ser1821Pro
NP_001341827.1:p.Ser1786Pro
NP_001341828.1:p.Ser1783Pro
NP_001341829.1:p.Ser1770Pro
NP_001341830.1:p.Ser1752Pro
NP_001341831.1:p.Ser1720Pro
NP_001341832.1:p.Ser1710Pro
NP_001341833.1:p.Ser1685Pro
NP_001341834.1:p.Ser1651Pro
NP_001341835.1:p.Ser1528Pro
LRG_130:g.153505T>C
NC_000005.9:g.112176722T>C
NM_000038.5:c.5431T>C

Protein change:

S1528P

Links:

dbSNP: rs777788406

NCBI 1000 Genomes Browser:

rs777788406

Molecular consequence:

NM_000038.6:c.5431T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.5431T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.5377T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.5431T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.5485T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.5461T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.5356T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.5347T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.5308T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.5254T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.5158T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.5128T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.5053T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.4951T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.4582T>C - 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
SCV000828958	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 30, 2020)	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

SCV000828958

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 30, 2020)

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, SCV000828958.3

#	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 serine with proline at codon 1811 of the APC protein (p.Ser1811Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. This variant is present in population databases (rs777788406, ExAC 0.01%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 438882). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The proline amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

#	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: Apr 23, 2022

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