NM_004360.5(CDH1):c.1008G>T (p.Glu336Asp) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 18, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000572541.5

Allele description [Variation Report for NM_004360.5(CDH1):c.1008G>T (p.Glu336Asp)]

NM_004360.5(CDH1):c.1008G>T (p.Glu336Asp)

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.1008G>T (p.Glu336Asp)

Other names:

NM_004360.4(CDH1):c.1008G>T

HGVS:

NC_000016.10:g.68811859G>T
NG_008021.1:g.79568G>T
NM_001317184.2:c.1008G>T
NM_001317185.2:c.-608G>T
NM_001317186.2:c.-812G>T
NM_004360.5:c.1008G>TMANE SELECT
NP_001304113.1:p.Glu336Asp
NP_004351.1:p.Glu336Asp
LRG_301t1:c.1008G>T
LRG_301:g.79568G>T
NC_000016.9:g.68845762G>T
NM_004360.3:c.1008G>T
P12830:p.Glu336Asp

Nucleotide change:

1008G-T

Protein change:

E336D

Links:

UniProtKB: P12830#VAR_001310; OMIM: 192090.0005; dbSNP: rs267606712

NCBI 1000 Genomes Browser:

rs267606712

Molecular consequence:

NM_001317185.2:c.-608G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317186.2:c.-812G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.1008G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.1008G>T - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000665108	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jun 18, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19223545, 23709761, 9537325 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000665108

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jun 18, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

E-cadherin deficiency initiates gastric signet-ring cell carcinoma in mice and man.

Humar B, Blair V, Charlton A, More H, Martin I, Guilford P.

Cancer Res. 2009 Mar 1;69(5):2050-6. doi: 10.1158/0008-5472.CAN-08-2457. Epub 2009 Feb 17.

PubMed [citation]

PMID:: 19223545

CDH1 germline mutations and the hereditary diffuse gastric and lobular breast cancer syndrome: a multicentre study.

Benusiglio PR, Malka D, Rouleau E, De Pauw A, Buecher B, Noguès C, Fourme E, Colas C, Coulet F, Warcoin M, Grandjouan S, Sezeur A, Laurent-Puig P, Molière D, Tlemsani C, Di Maria M, Byrde V, Delaloge S, Blayau M, Caron O.

J Med Genet. 2013 Jul;50(7):486-9. doi: 10.1136/jmedgenet-2012-101472. Epub 2013 May 25.

PubMed [citation]

PMID:: 23709761

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000665108.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.1008G>T pathogenic mutation (also known as p.E336D), located in coding exon 7 of the CDH1 gene, results from a G to T substitution at nucleotide position 1008. This change occurs in the last base pair of coding exon 7, which makes it likely to have some effect on normal mRNA splicing. In addition to potential splicing impact, this alteration changes the glutamic acid at codon 336 to aspartic acid, an amino acid with highly similar properties. This alteration segregated with disease in a family with hereditary diffuse gastric cancer, and RT-PCR studies demonstrated a 7 base pair insertion between the normal splice donor site and an adjacent cryptic splice site (Guilford P et al. Nature 1998 Mar;392:402-5). Internal RNA splicing analyses confirmed this out-of-frame 7 base pair insertion and showed additional out-of-frame transcripts containing a 25 base pair insertion and an insertion of intron 7 (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

ClinVar

Relating variation to medicine