NM_004360.5(CDH1):c.353C>G (p.Thr118Arg) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 18, 2023
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:: RCV002512549.2

Allele description [Variation Report for NM_004360.5(CDH1):c.353C>G (p.Thr118Arg)]

NM_004360.5(CDH1):c.353C>G (p.Thr118Arg)

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.353C>G (p.Thr118Arg)

HGVS:

NC_000016.10:g.68801859C>G
NG_008021.1:g.69568C>G
NM_001317184.2:c.353C>G
NM_001317185.2:c.-1263C>G
NM_001317186.2:c.-1467C>G
NM_004360.5:c.353C>GMANE SELECT
NP_001304113.1:p.Thr118Arg
NP_004351.1:p.Thr118Arg
LRG_301t1:c.353C>G
LRG_301:g.69568C>G
NC_000016.9:g.68835762C>G
NM_004360.3:c.353C>G
p.T118R

Protein change:

T118R

Links:

dbSNP: rs587782677

NCBI 1000 Genomes Browser:

rs587782677

Molecular consequence:

NM_001317185.2:c.-1263C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317186.2:c.-1467C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.353C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.353C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary diffuse gastric adenocarcinoma (HDGC)
Synonyms:: Hereditary diffuse gastric cancer
Identifiers:: MONDO: MONDO:0007648; MedGen: C1708349; Orphanet: 26106; OMIM: 137215

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003443609	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 18, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17221870, 19268661, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003443609

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 18, 2023)

germline

clinical testing

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

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

Identification of seven novel germline mutations in the human E-cadherin (CDH1) gene.

More H, Humar B, Weber W, Ward R, Christian A, Lintott C, Graziano F, Ruzzo AM, Acosta E, Boman B, Harlan M, Ferreira P, Seruca R, Suriano G, Guilford P.

Hum Mutat. 2007 Feb;28(2):203.

PubMed [citation]

PMID:: 17221870

E-cadherin mutations and cell motility: a genotype-phenotype correlation.

Mateus AR, Simões-Correia J, Figueiredo J, Heindl S, Alves CC, Suriano G, Luber B, Seruca R.

Exp Cell Res. 2009 May 1;315(8):1393-402. doi: 10.1016/j.yexcr.2009.02.020. Epub 2009 Mar 4.

PubMed [citation]

PMID:: 19268661

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003443609.2

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

Description

This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 118 of the CDH1 protein (p.Thr118Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with diffuse gastric cancer (PMID: 17221870). ClinVar contains an entry for this variant (Variation ID: 142730). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CDH1 function (PMID: 17221870, 19268661). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: May 1, 2024

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