NM_004360.5(CDH1):c.1570C>T (p.Arg524Trp) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 3, 2024
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:: RCV000481206.6

Allele description [Variation Report for NM_004360.5(CDH1):c.1570C>T (p.Arg524Trp)]

NM_004360.5(CDH1):c.1570C>T (p.Arg524Trp)

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.1570C>T (p.Arg524Trp)

HGVS:

NC_000016.10:g.68819284C>T
NG_008021.1:g.86993C>T
NM_001317184.2:c.1387C>T
NM_001317185.2:c.22C>T
NM_001317186.2:c.-254-2717C>T
NM_004360.5:c.1570C>TMANE SELECT
NP_001304113.1:p.Arg463Trp
NP_001304114.1:p.Arg8Trp
NP_004351.1:p.Arg524Trp
LRG_301t1:c.1570C>T
LRG_301:g.86993C>T
NC_000016.9:g.68853187C>T
NM_004360.3:c.1570C>T
NM_004360.4:c.1570C>T

Protein change:

R463W

Links:

dbSNP: rs373605261

NCBI 1000 Genomes Browser:

rs373605261

Molecular consequence:

NM_001317186.2:c.-254-2717C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001317184.2:c.1387C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001317185.2:c.22C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.1570C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Agrianome fairmairei isolate NG04 NADH dehydrogenase subunit 2 (ND2) gene, parti...
Agrianome fairmairei isolate NG04 NADH dehydrogenase subunit 2 (ND2) gene, partial cds; mitochondrial
gi|2772184590|gb|OR579790.1|

Nucleotide
Aidanosagitta regularis voucher NIOBZC28 cytochrome oxidase subunit I (COI) gene...
Aidanosagitta regularis voucher NIOBZC28 cytochrome oxidase subunit I (COI) gene, partial cds; mitochondrial
gi|359744748|gb|JN258028.1|

Nucleotide

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
SCV000566063	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 3, 2024)	germline	clinical testing	Citation Link,
SCV001134061	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Dec 22, 2022)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27904775, 33471991, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000566063

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 3, 2024)

germline

clinical testing

Citation Link,

SCV001134061

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Dec 22, 2022)

unknown

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Disease evolution and heterogeneity in bilateral breast cancer.

Fountzilas E, Kotoula V, Zagouri F, Giannoulatou E, Kouvatseas G, Pentheroudakis G, Koletsa T, Bobos M, Papadopoulou K, Samantas E, Demiri E, Miliaras S, Christodoulou C, Chrisafi S, Razis E, Fostira F, Pectasides D, Zografos G, Fountzilas G.

Am J Cancer Res. 2016;6(11):2611-2630.

PubMed [citation]

PMID:: 27904775
PMCID:: PMC5126277

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

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000566063.6

#	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 supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27904775, 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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001134061.4

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

Description

The frequency of this variant in the general population, 0.000004 (1/251482 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. This variant has only been reported as a somatic variant in bilateral breast tumors (PMID: 27904775 (2016)). In a large-scale breast cancer association study, the variant was observed in an unaffected individual (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/CDH1)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine