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NM_004360.5(CDH1):c.1334A>C (p.Glu445Ala)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Jun 11, 2021)
Last evaluated:
Dec 21, 2020
Accession:
VCV000127911.10
Variation ID:
127911
Description:
single nucleotide variant
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NM_004360.5(CDH1):c.1334A>C (p.Glu445Ala)

Allele ID
133368
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
16q22.1
Genomic location
16: 68815528 (GRCh38) GRCh38 UCSC
16: 68849431 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000016.10:g.68815528A>C
NC_000016.9:g.68849431A>C
NM_004360.5:c.1334A>C MANE Select NP_004351.1:p.Glu445Ala missense
... more HGVS
Protein change
E445A, E384A
Other names
p.E445A:GAG>GCG
Canonical SPDI
NC_000016.10:68815527:A:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00006
Exome Aggregation Consortium (ExAC) 0.00001
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
The Genome Aggregation Database (gnomAD), exomes 0.00001
Links
ClinGen: CA288031
dbSNP: rs374398608
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Oct 20, 2020 RCV000123235.8
Uncertain significance 1 criteria provided, single submitter Jun 29, 2018 RCV000212366.2
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Dec 21, 2020 RCV000115839.11
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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
(Jun 29, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000149748.14
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted CDH1 c.1334A>C at the cDNA level, p.Glu445Ala (E445A) at the protein level, and results in the change of a Glutamic Acid … (more)
Likely benign
(Sep 28, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000186103.6
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
Other strong data supporting benign classification
Uncertain significance
(Oct 20, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary diffuse gastric cancer
Allele origin: germline
Invitae
Accession: SCV000166541.8
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces glutamic acid with alanine at codon 445 of the CDH1 protein (p.Glu445Ala). The glutamic acid residue is highly conserved and there … (more)
Uncertain significance
(Dec 21, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000684353.4
Submitted: (Jun 11, 2021)
Evidence details
Comment:
This missense variant replaces glutamic acid with alanine at codon 445 of the CDH1 protein. To our knowledge, functional studies have not been reported for … (more)
Uncertain significance
(Sep 11, 2017)
no assertion criteria provided
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
True Health Diagnostics
Accession: SCV000787975.1
Submitted: (Mar 08, 2018)
Evidence details

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
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
Frequent germline deleterious mutations in DNA repair genes in familial prostate cancer cases are associated with advanced disease. Leongamornlert D British journal of cancer 2014 PMID: 24556621

Text-mined citations for rs374398608...

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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 19, 2021