NM_004360.5(CDH1):c.1679C>G (p.Thr560Arg) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 16, 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:: RCV003477778.1

Allele description [Variation Report for NM_004360.5(CDH1):c.1679C>G (p.Thr560Arg)]

NM_004360.5(CDH1):c.1679C>G (p.Thr560Arg)

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.1679C>G (p.Thr560Arg)

Other names:

NM_004360.4(CDH1):c.1679C>G

HGVS:

NC_000016.10:g.68819393C>G
NG_008021.1:g.87102C>G
NM_001317184.2:c.1496C>G
NM_001317185.2:c.131C>G
NM_001317186.2:c.-254-2608C>G
NM_004360.5:c.1679C>GMANE SELECT
NP_001304113.1:p.Thr499Arg
NP_001304114.1:p.Thr44Arg
NP_004351.1:p.Thr560Arg
LRG_301t1:c.1679C>G
LRG_301:g.87102C>G
NC_000016.9:g.68853296C>G
NM_004360.3:c.1679C>G
NM_004360.4:c.1679C>G

Protein change:

T44R

Links:

dbSNP: rs746481984

NCBI 1000 Genomes Browser:

rs746481984

Molecular consequence:

NM_001317186.2:c.-254-2608C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001317184.2:c.1496C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001317185.2:c.131C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.1679C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004220801	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jun 16, 2023)	unknown	clinical testing	PubMed (9) [See all records that cite these PMIDs] 33471991, 36436516, 34949788, 33268956, 30745422, 29769627, 27880784, 23709761, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004220801

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Jun 16, 2023)

unknown

clinical testing

PubMed (9)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]

PMID:: 33471991
PMCID:: PMC7611105

Genotype-first approach to identify associations between CDH1 germline variants and cancer phenotypes: a multicentre study by the European Reference Network on Genetic Tumour Risk Syndromes.

Garcia-Pelaez J, Barbosa-Matos R, Lobo S, Dias A, Garrido L, Castedo S, Sousa S, Pinheiro H, Sousa L, Monteiro R, Maqueda JJ, Fernandes S, Carneiro F, Pinto N, Lemos C, Pinto C, Teixeira MR, Aretz S, Bajalica-Lagercrantz S, Balmaña J, Blatnik A, Benusiglio PR, et al.

Lancet Oncol. 2023 Jan;24(1):91-106. doi: 10.1016/S1470-2045(22)00643-X. Epub 2022 Nov 24. Erratum in: Lancet Oncol. 2023 Jan;24(1):e10. doi: 10.1016/S1470-2045(22)00761-6.

PubMed [citation]

PMID:: 36436516
PMCID:: PMC9810541

See all PubMed Citations (9)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004220801.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The CDH1 c.1679C>G (p.Thr560Arg) variant activates a cryptic splice donor site and has been shown in the published literature to cause aberrant mRNA splicing and the production of a truncated CDH1 transcript (PMID: 27880784 (2016)). Further experimental studies showed this variant has deleterious effects on CDH1 protein function (PMID: 29769627 (2018)). This variant has been reported in multiple individuals with diffused gastric cancer and lobular breast cancer (PMIDs: 36436516 (2022), 34949788 (2022), 29769627 (2018), 23709761 (2013)), and segregated with disease in at least two families with HDGC (PMIDs: 33268956 (2020), 27880784 (2016)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.

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

Last Updated: Jul 15, 2024

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