NM_004360.5(CDH1):c.2603G>A (p.Arg868His) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 14, 2022
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:: RCV001824693.9

Allele description [Variation Report for NM_004360.5(CDH1):c.2603G>A (p.Arg868His)]

NM_004360.5(CDH1):c.2603G>A (p.Arg868His)

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.2603G>A (p.Arg868His)

HGVS:

NC_000016.10:g.68833453G>A
NG_008021.1:g.101162G>A
NM_001317184.2:c.2420G>A
NM_001317185.2:c.1055G>A
NM_001317186.2:c.638G>A
NM_004360.5:c.2603G>AMANE SELECT
NP_001304113.1:p.Arg807His
NP_001304114.1:p.Arg352His
NP_001304115.1:p.Arg213His
NP_004351.1:p.Arg868His
LRG_301t1:c.2603G>A
LRG_301:g.101162G>A
NC_000016.9:g.68867356G>A
NM_001317185.1:c.1055G>A
NM_004360.3:c.2603G>A
NM_004360.4:c.2603G>A

Protein change:

R213H

Links:

dbSNP: rs369126891

NCBI 1000 Genomes Browser:

rs369126891

Molecular consequence:

NM_001317184.2:c.2420G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001317185.2:c.1055G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001317186.2:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.2603G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002074264	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jan 14, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30287823, 32068069, 33471991 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002074264

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jan 14, 2022)

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

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.

Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, Katagiri T, Yoshida T, Nakamura S, Sugano K, Miki Y, Hirata M, Matsuda K, Spurdle AB, Kubo M.

Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8.

PubMed [citation]

PMID:: 30287823
PMCID:: PMC6172276

Germline Mutation in 1338 BRCA-Negative Chinese Hereditary Breast and/or Ovarian Cancer Patients: Clinical Testing with a Multigene Test Panel.

Kwong A, Shin VY, Chen J, Cheuk IWY, Ho CYS, Au CH, Chan KKL, Ngan HYS, Chan TL, Ford JM, Ma ESK.

J Mol Diagn. 2020 Apr;22(4):544-554. doi: 10.1016/j.jmoldx.2020.01.013. Epub 2020 Feb 15.

PubMed [citation]

PMID:: 32068069

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002074264.1

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

Description

Variant summary: CDH1 c.2603G>A (p.Arg868His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.8e-05 in 273948 control chromosomes (gnomAD, Momozawa_2018). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2603G>A has been reported in the literature in individuals affected with Breast Cancer (example: Dorling_2021, Kwong_2020). These reports do not provide unequivocal conclusions about association of the variant with Breast Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitters have assessed the variant since 2014: all submitters classified the variant as of uncertain significance. Based on the evidence outlined above, the variant was classified as 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: Nov 10, 2024

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