U.S. flag

An official website of the United States government

NM_000038.6(APC):c.3341G>A (p.Arg1114Gln) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Oct 14, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000574225.12

Allele description [Variation Report for NM_000038.6(APC):c.3341G>A (p.Arg1114Gln)]

NM_000038.6(APC):c.3341G>A (p.Arg1114Gln)

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.3341G>A (p.Arg1114Gln)
HGVS:
  • NC_000005.10:g.112838935G>A
  • NG_008481.4:g.151415G>A
  • NM_000038.6:c.3341G>AMANE SELECT
  • NM_001127510.3:c.3341G>A
  • NM_001127511.3:c.3287G>A
  • NM_001354895.2:c.3341G>A
  • NM_001354896.2:c.3395G>A
  • NM_001354897.2:c.3371G>A
  • NM_001354898.2:c.3266G>A
  • NM_001354899.2:c.3257G>A
  • NM_001354900.2:c.3218G>A
  • NM_001354901.2:c.3164G>A
  • NM_001354902.2:c.3068G>A
  • NM_001354903.2:c.3038G>A
  • NM_001354904.2:c.2963G>A
  • NM_001354905.2:c.2861G>A
  • NM_001354906.2:c.2492G>A
  • NP_000029.2:p.Arg1114Gln
  • NP_001120982.1:p.Arg1114Gln
  • NP_001120983.2:p.Arg1096Gln
  • NP_001341824.1:p.Arg1114Gln
  • NP_001341825.1:p.Arg1132Gln
  • NP_001341826.1:p.Arg1124Gln
  • NP_001341827.1:p.Arg1089Gln
  • NP_001341828.1:p.Arg1086Gln
  • NP_001341829.1:p.Arg1073Gln
  • NP_001341830.1:p.Arg1055Gln
  • NP_001341831.1:p.Arg1023Gln
  • NP_001341832.1:p.Arg1013Gln
  • NP_001341833.1:p.Arg988Gln
  • NP_001341834.1:p.Arg954Gln
  • NP_001341835.1:p.Arg831Gln
  • LRG_130:g.151415G>A
  • NC_000005.9:g.112174632G>A
  • NM_000038.5:c.3341G>A
Protein change:
R1013Q
Links:
dbSNP: rs753209586
NCBI 1000 Genomes Browser:
rs753209586
Molecular consequence:
  • NM_000038.6:c.3341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127510.3:c.3341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127511.3:c.3287G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354895.2:c.3341G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354896.2:c.3395G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354897.2:c.3371G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354898.2:c.3266G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354899.2:c.3257G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354900.2:c.3218G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354901.2:c.3164G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354902.2:c.3068G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354903.2:c.3038G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354904.2:c.2963G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354905.2:c.2861G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354906.2:c.2492G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000667750Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)
Uncertain significance
(Oct 14, 2022)
germlineclinical testing

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

Citation Link,

SCV004362105Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Sep 12, 2022)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Ambry Genetics, SCV000667750.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.R1114Q variant (also known as c.3341G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 3341. The arginine at codon 1114 is replaced by glutamine, an amino acid with highly similar properties. This alteration was identified in an cohort of 1058 unselected individuals with colon cancer (Yurgelun MB et al. J. Clin. Oncol. 2017 Apr;35:1086-1095). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV004362105.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This missense variant replaces arginine with glutamine at codon 1114 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with colon cancer in the literature (PMID: 28135145). This variant has been identified in 5/281838 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Apr 20, 2024