NM_004360.5(CDH1):c.1136C>T (p.Thr379Met) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 14, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000480330.4

Allele description [Variation Report for NM_004360.5(CDH1):c.1136C>T (p.Thr379Met)]

NM_004360.5(CDH1):c.1136C>T (p.Thr379Met)

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.1136C>T (p.Thr379Met)

Other names:

NM_001317186.2:c.-684C>T

HGVS:

NC_000016.10:g.68812262C>T
NG_008021.1:g.79971C>T
NM_001317184.2:c.1136C>T
NM_001317185.2:c.-480C>T
NM_001317186.2:c.-684C>T
NM_004360.5:c.1136C>TMANE SELECT
NP_001304113.1:p.Thr379Met
NP_004351.1:p.Thr379Met
LRG_301t1:c.1136C>T
LRG_301:g.79971C>T
NC_000016.9:g.68846165C>T
NM_004360.3:c.1136C>T
NM_004360.4:c.1136C>T
p.T379M

Protein change:

T379M

Links:

dbSNP: rs587782856

NCBI 1000 Genomes Browser:

rs587782856

Molecular consequence:

NM_001317185.2:c.-480C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317186.2:c.-684C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.1136C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.1136C>T - 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
SCV000567843	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Dec 2, 2022)	germline	clinical testing	Citation Link,
SCV004563165	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Uncertain significance (Sep 14, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000567843

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Dec 2, 2022)

germline

clinical testing

Citation Link,

SCV004563165

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Uncertain significance
(Sep 14, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000567843.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30836094, 30766968, 31871109, 15235021, 22850631)

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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV004563165.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The CDH1 c.1136C>T; p.Thr379Met variant (rs587782856) is reported in the literature in individuals affected with cancer (Garcia-Pelaez 2023, Guindalini 2022). This variant is reported in ClinVar (Variation ID: 142968), and is found in the general population with an overall allele frequency of 0.002% (4/251,460 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is neutral (REVEL: 0.03). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Garcia-Pelaez J et al. 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. Lancet Oncol. 2023 Jan;24(1):91-106. PMID: 36436516. Guindalini RSC et al. Detection of germline variants in Brazilian breast cancer patients using multigene panel testing. Sci Rep. 2022 Mar 9;12(1):4190. PMID: 35264596.

#	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: Sep 29, 2024

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