U.S. flag

An official website of the United States government

NM_000038.6(APC):c.5975C>T (p.Pro1992Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 27, 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:
RCV001024737.11

Allele description [Variation Report for NM_000038.6(APC):c.5975C>T (p.Pro1992Leu)]

NM_000038.6(APC):c.5975C>T (p.Pro1992Leu)

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.5975C>T (p.Pro1992Leu)
HGVS:
  • NC_000005.10:g.112841569C>T
  • NG_008481.4:g.154049C>T
  • NM_000038.6:c.5975C>TMANE SELECT
  • NM_001127510.3:c.5975C>T
  • NM_001127511.3:c.5921C>T
  • NM_001354895.2:c.5975C>T
  • NM_001354896.2:c.6029C>T
  • NM_001354897.2:c.6005C>T
  • NM_001354898.2:c.5900C>T
  • NM_001354899.2:c.5891C>T
  • NM_001354900.2:c.5852C>T
  • NM_001354901.2:c.5798C>T
  • NM_001354902.2:c.5702C>T
  • NM_001354903.2:c.5672C>T
  • NM_001354904.2:c.5597C>T
  • NM_001354905.2:c.5495C>T
  • NM_001354906.2:c.5126C>T
  • NP_000029.2:p.Pro1992Leu
  • NP_001120982.1:p.Pro1992Leu
  • NP_001120983.2:p.Pro1974Leu
  • NP_001341824.1:p.Pro1992Leu
  • NP_001341825.1:p.Pro2010Leu
  • NP_001341826.1:p.Pro2002Leu
  • NP_001341827.1:p.Pro1967Leu
  • NP_001341828.1:p.Pro1964Leu
  • NP_001341829.1:p.Pro1951Leu
  • NP_001341830.1:p.Pro1933Leu
  • NP_001341831.1:p.Pro1901Leu
  • NP_001341832.1:p.Pro1891Leu
  • NP_001341833.1:p.Pro1866Leu
  • NP_001341834.1:p.Pro1832Leu
  • NP_001341835.1:p.Pro1709Leu
  • LRG_130:g.154049C>T
  • NC_000005.9:g.112177266C>T
  • NM_000038.5:c.5975C>T
Protein change:
P1709L
Links:
dbSNP: rs1580666303
NCBI 1000 Genomes Browser:
rs1580666303
Molecular consequence:
  • NM_000038.6:c.5975C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127510.3:c.5975C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127511.3:c.5921C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354895.2:c.5975C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354896.2:c.6029C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354897.2:c.6005C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354898.2:c.5900C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354899.2:c.5891C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354900.2:c.5852C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354901.2:c.5798C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354902.2:c.5702C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354903.2:c.5672C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354904.2:c.5597C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354905.2:c.5495C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354906.2:c.5126C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001186809Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Oct 27, 2022) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S.

J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.

PubMed [citation]
PMID:
28135145
PMCID:
PMC5455355

Details of each submission

From Ambry Genetics, SCV001186809.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The p.P1992L variant (also known as c.5975C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 5975. The proline at codon 1992 is replaced by leucine, an amino acid with similar properties. This variant was identified in a cohort of 1058 individuals with colorectal cancer undergoing panel testing for hereditary cancer susceptibility (Yurgelun MB et al. J. Clin. Oncol., 2017 Apr;35:1086-1095). This amino acid position is not well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024