NM_000038.6(APC):c.4372C>T (p.Pro1458Ser) AND Familial adenomatous polyposis 1

Germline classification:: Conflicting classifications of pathogenicity (3 submissions)
Last evaluated:: Jan 30, 2025
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:: RCV000196865.29

Allele description [Variation Report for NM_000038.6(APC):c.4372C>T (p.Pro1458Ser)]

NM_000038.6(APC):c.4372C>T (p.Pro1458Ser)

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.4372C>T (p.Pro1458Ser)

Other names:

p.P1458S:CCT>TCT

HGVS:

NC_000005.10:g.112839966C>T
NG_008481.4:g.152446C>T
NM_000038.6:c.4372C>TMANE SELECT
NM_001127510.3:c.4372C>T
NM_001127511.3:c.4318C>T
NM_001354895.2:c.4372C>T
NM_001354896.2:c.4426C>T
NM_001354897.2:c.4402C>T
NM_001354898.2:c.4297C>T
NM_001354899.2:c.4288C>T
NM_001354900.2:c.4249C>T
NM_001354901.2:c.4195C>T
NM_001354902.2:c.4099C>T
NM_001354903.2:c.4069C>T
NM_001354904.2:c.3994C>T
NM_001354905.2:c.3892C>T
NM_001354906.2:c.3523C>T
NP_000029.2:p.Pro1458Ser
NP_001120982.1:p.Pro1458Ser
NP_001120983.2:p.Pro1440Ser
NP_001341824.1:p.Pro1458Ser
NP_001341825.1:p.Pro1476Ser
NP_001341826.1:p.Pro1468Ser
NP_001341827.1:p.Pro1433Ser
NP_001341828.1:p.Pro1430Ser
NP_001341829.1:p.Pro1417Ser
NP_001341830.1:p.Pro1399Ser
NP_001341831.1:p.Pro1367Ser
NP_001341832.1:p.Pro1357Ser
NP_001341833.1:p.Pro1332Ser
NP_001341834.1:p.Pro1298Ser
NP_001341835.1:p.Pro1175Ser
LRG_130:g.152446C>T
NC_000005.9:g.112175663C>T
NM_000038.5:c.4372C>T
p.P1458S

Protein change:

P1175S

Links:

dbSNP: rs143796828

NCBI 1000 Genomes Browser:

rs143796828

Molecular consequence:

NM_000038.6:c.4372C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.4372C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.4318C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.4372C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.4426C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.4402C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.4297C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.4288C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.4249C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.4195C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.4099C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.4069C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.3994C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.3892C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.3523C>T - 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
SCV000254014	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 30, 2025)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000488485	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Uncertain significance (Apr 14, 2016)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22703879, 18199528 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV004018790	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Uncertain significance (Feb 22, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000254014

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 30, 2025)

germline

clinical testing

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

SCV000488485

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))

Uncertain significance
(Apr 14, 2016)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV004018790

Myriad Genetics, Inc.

criteria provided, single submitter

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

Uncertain significance
(Feb 22, 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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes.

Johnston JJ, Rubinstein WS, Facio FM, Ng D, Singh LN, Teer JK, Mullikin JC, Biesecker LG.

Am J Hum Genet. 2012 Jul 13;91(1):97-108. doi: 10.1016/j.ajhg.2012.05.021. Epub 2012 Jun 14.

PubMed [citation]

PMID:: 22703879
PMCID:: PMC3397257

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000254014.13

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Counsyl, SCV000488485.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	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 Myriad Genetics, Inc., SCV004018790.1

#	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 classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

#	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: Feb 25, 2025

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