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NM_004360.5(CDH1):c.1004G>A (p.Arg335Gln)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(6)

Review status:
criteria provided, conflicting interpretations
Submissions:
7 (Most recent: Jan 7, 2021)
Last evaluated:
Nov 1, 2020
Accession:
VCV000127905.10
Variation ID:
127905
Description:
single nucleotide variant
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NM_004360.5(CDH1):c.1004G>A (p.Arg335Gln)

Allele ID
133362
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
16q22.1
Genomic location
16: 68811855 (GRCh38) GRCh38 UCSC
16: 68845758 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000016.9:g.68845758G>A
NC_000016.10:g.68811855G>A
NM_004360.5:c.1004G>A MANE Select NP_004351.1:p.Arg335Gln missense
... more HGVS
Protein change
R335Q
Other names
p.R335Q:CGA>CAA
Canonical SPDI
NC_000016.10:68811854:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (A)

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00004
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00002
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Links
ClinGen: CA288013
dbSNP: rs373364873
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 3 criteria provided, multiple submitters, no conflicts Nov 1, 2020 RCV000229894.8
Uncertain significance 1 criteria provided, single submitter Oct 8, 2018 RCV000586292.3
Uncertain significance 1 criteria provided, single submitter Sep 6, 2019 RCV000855585.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Sep 11, 2020 RCV000115832.10
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CDH1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
2747 2787

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Oct 08, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000149741.15
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted CDH1 c.1004G>A at the cDNA level, p.Arg335Gln (R335Q) at the protein level, and results in the change of an Arginine to … (more)
Uncertain significance
(Dec 04, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000684319.3
Submitted: (May 19, 2020)
Comment:
This missense variant replaces arginine with glutamine at codon 335 of the CDH1 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
Evidence details
Likely benign
(Sep 11, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000185512.6
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
Other strong data supporting benign classification
Uncertain significance
(Nov 01, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary diffuse gastric cancer
Allele origin: germline
Invitae
Accession: SCV000288411.8
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces arginine with glutamine at codon 335 of the CDH1 protein (p.Arg335Gln). The arginine residue is highly conserved and there is a … (more)
Uncertain significance
(Feb 12, 2016)
criteria provided, single submitter
Method: clinical testing
Hereditary diffuse gastric cancer
Allele origin: unknown
Counsyl
Accession: SCV000488287.1
Submitted: (Nov 23, 2016)
Evidence details
Publications
PubMed (2)
Uncertain significance
(Jul 02, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary diffuse gastric cancer
Allele origin: unknown
Mendelics
Accession: SCV000839085.1
Submitted: (Aug 20, 2018)
Evidence details
Uncertain significance
(Sep 06, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698351.2
Submitted: (Sep 24, 2019)
Evidence details
Publications
PubMed (4)
Comment:
Variant summary: CDH1 c.1004G>A (p.Arg335Gln) results in a conservative amino acid change located in the Cadherin-like (IPR002126) of the encoded protein sequence. Four of five … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. Momozawa Y Nature communications 2018 PMID: 30287823
Targeted sequencing of established and candidate colorectal cancer genes in the Colon Cancer Family Registry Cohort. Raskin L Oncotarget 2017 PMID: 29212164
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Relationship between E-cadherin gene mutation and p53 gene mutation, p53 accumulation, Bcl-2 expression and Ki-67 staining in diffuse-type gastric carcinoma. Fricke E International journal of cancer 2003 PMID: 12532420
Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer. Rosivatz E The American journal of pathology 2002 PMID: 12414534

Text-mined citations for rs373364873...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 14, 2021