NM_000038.6(APC):c.4732T>G (p.Cys1578Gly) AND Hereditary cancer-predisposing syndrome

Clinical significance:Likely pathogenic (Last evaluated: Jul 29, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000129037.6

Allele description [Variation Report for NM_000038.6(APC):c.4732T>G (p.Cys1578Gly)]

NM_000038.6(APC):c.4732T>G (p.Cys1578Gly)

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.4732T>G (p.Cys1578Gly)
HGVS:
  • NC_000005.10:g.112840326T>G
  • NG_008481.4:g.152806T>G
  • NM_000038.6:c.4732T>GMANE SELECT
  • NM_001127510.3:c.4732T>G
  • NM_001127511.3:c.4678T>G
  • NM_001354895.2:c.4732T>G
  • NM_001354896.2:c.4786T>G
  • NM_001354897.2:c.4762T>G
  • NM_001354898.2:c.4657T>G
  • NM_001354899.2:c.4648T>G
  • NM_001354900.2:c.4609T>G
  • NM_001354901.2:c.4555T>G
  • NM_001354902.2:c.4459T>G
  • NM_001354903.2:c.4429T>G
  • NM_001354904.2:c.4354T>G
  • NM_001354905.2:c.4252T>G
  • NM_001354906.2:c.3883T>G
  • NP_000029.2:p.Cys1578Gly
  • NP_001120982.1:p.Cys1578Gly
  • NP_001120983.2:p.Cys1560Gly
  • NP_001341824.1:p.Cys1578Gly
  • NP_001341825.1:p.Cys1596Gly
  • NP_001341826.1:p.Cys1588Gly
  • NP_001341827.1:p.Cys1553Gly
  • NP_001341828.1:p.Cys1550Gly
  • NP_001341829.1:p.Cys1537Gly
  • NP_001341830.1:p.Cys1519Gly
  • NP_001341831.1:p.Cys1487Gly
  • NP_001341832.1:p.Cys1477Gly
  • NP_001341833.1:p.Cys1452Gly
  • NP_001341834.1:p.Cys1418Gly
  • NP_001341835.1:p.Cys1295Gly
  • LRG_130:g.152806T>G
  • NC_000005.9:g.112176023T>G
  • NM_000038.5:c.4732T>G
  • NM_001127510.2:c.4732T>G
  • p.C1578G
Protein change:
C1295G
Links:
dbSNP: rs138367627
NCBI 1000 Genomes Browser:
rs138367627
Molecular consequence:
  • NM_000038.6:c.4732T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127510.3:c.4732T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127511.3:c.4678T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354895.2:c.4732T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354896.2:c.4786T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354897.2:c.4762T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354898.2:c.4657T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354899.2:c.4648T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354900.2:c.4609T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354901.2:c.4555T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354902.2:c.4459T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354903.2:c.4429T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354904.2:c.4354T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354905.2:c.4252T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354906.2:c.3883T>G - 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; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000172947Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Jul 29, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Structural basis of the Axin-adenomatous polyposis coli interaction.

Spink KE, Polakis P, Weis WI.

EMBO J. 2000 May 15;19(10):2270-9.

PubMed [citation]
PMID:
10811618
PMCID:
PMC384355

Multiple rare nonsynonymous variants in the adenomatous polyposis coli gene predispose to colorectal adenomas.

Azzopardi D, Dallosso AR, Eliason K, Hendrickson BC, Jones N, Rawstorne E, Colley J, Moskvina V, Frye C, Sampson JR, Wenstrup R, Scholl T, Cheadle JP.

Cancer Res. 2008 Jan 15;68(2):358-63. doi: 10.1158/0008-5472.CAN-07-5733.

PubMed [citation]
PMID:
18199528
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000172947.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (5)

Description

The p.C1578G variant (also known as c.4732T>G), located in coding exon 15 of the APC gene, results from a T to G substitution at nucleotide position 4732. The cysteine at codon 1578 is replaced by glycine, an amino acid with highly dissimilar properties. This variant has been detected in an individual with 11-99 colorectal adenomas, and it is located in a conserved SAMP repeat that functions as an axin binding domain (Azzopardi et al. Cancer Res. 2008 Jan;68:358-63; Minde DP et al. Mol. Cancer. 2011 Aug;10:101; Spink KE et al. EMBO J. 2000 May;19:2270–9). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Nov 27, 2021

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