NM_004360.5(CDH1):c.1793G>A (p.Arg598Gln) AND Hereditary cancer-predisposing syndrome

Germline classification:
Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:
Aug 17, 2022
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:
RCV000216786.14

Allele description [Variation Report for NM_004360.5(CDH1):c.1793G>A (p.Arg598Gln)]

NM_004360.5(CDH1):c.1793G>A (p.Arg598Gln)

Gene:
CDH1:cadherin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q22.1
Genomic location:
Preferred name:
NM_004360.5(CDH1):c.1793G>A (p.Arg598Gln)
HGVS:
  • NC_000016.10:g.68822082G>A
  • NG_008021.1:g.89791G>A
  • NM_001317184.2:c.1610G>A
  • NM_001317185.2:c.245G>A
  • NM_001317186.2:c.-173G>A
  • NM_004360.5:c.1793G>AMANE SELECT
  • NP_001304113.1:p.Arg537Gln
  • NP_001304114.1:p.Arg82Gln
  • NP_004351.1:p.Arg598Gln
  • LRG_301t1:c.1793G>A
  • LRG_301:g.89791G>A
  • NC_000016.9:g.68855985G>A
  • NM_004360.3:c.1793G>A
  • NM_004360.4:c.1793G>A
  • P12830:p.Arg598Gln
Protein change:
R537Q
Links:
UniProtKB: P12830#VAR_001319; dbSNP: rs780759537
NCBI 1000 Genomes Browser:
rs780759537
Molecular consequence:
  • NM_001317186.2:c.-173G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001317184.2:c.1610G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317185.2:c.245G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004360.5:c.1793G>A - 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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000275296Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely benign
(Apr 25, 2021) 		germlineclinical testing

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

Citation Link,

SCV000684381Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Aug 17, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

The genetic landscape of breast carcinomas with neuroendocrine differentiation.

Marchiò C, Geyer FC, Ng CK, Piscuoglio S, De Filippo MR, Cupo M, Schultheis AM, Lim RS, Burke KA, Guerini-Rocco E, Papotti M, Norton L, Sapino A, Weigelt B, Reis-Filho JS.

J Pathol. 2017 Feb;241(3):405-419. doi: 10.1002/path.4837. Epub 2016 Dec 26.

PubMed [citation]
PMID:
27925203
PMCID:
PMC5481202

Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.

Pritchard AL, Johansson PA, Nathan V, Howlie M, Symmons J, Palmer JM, Hayward NK.

PLoS One. 2018;13(4):e0194098. doi: 10.1371/journal.pone.0194098.

PubMed [citation]
PMID:
29641532
PMCID:
PMC5894988
See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV000275296.7

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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

From Color Diagnostics, LLC DBA Color Health, SCV000684381.6

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

Description

This missense variant replaces arginine with glutamine at codon 598 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been observed in a tumor sample from an individual with diffuse gastric cancer (PMID: 9744472, 10094558), in an individual affected with breast cancer (PMID 25186627) and in an unaffected control individual (PMID: 30287823). This variant has been identified in 7/282886 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: Feb 25, 2025