NM_004360.5(CDH1):c.1813A>G (p.Arg605Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 2, 2020
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:: RCV002406982.2

Allele description [Variation Report for NM_004360.5(CDH1):c.1813A>G (p.Arg605Gly)]

NM_004360.5(CDH1):c.1813A>G (p.Arg605Gly)

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.1813A>G (p.Arg605Gly)

HGVS:

NC_000016.10:g.68822102A>G
NG_008021.1:g.89811A>G
NM_001317184.2:c.1630A>G
NM_001317185.2:c.265A>G
NM_001317186.2:c.-153A>G
NM_004360.5:c.1813A>GMANE SELECT
NP_001304113.1:p.Arg544Gly
NP_001304114.1:p.Arg89Gly
NP_004351.1:p.Arg605Gly
LRG_301t1:c.1813A>G
LRG_301:g.89811A>G
NC_000016.9:g.68856005A>G
NM_004360.3:c.1813A>G

Protein change:

R544G

Links:

dbSNP: rs2152138356

NCBI 1000 Genomes Browser:

rs2152138356

Molecular consequence:

NM_001317186.2:c.-153A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.1630A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001317185.2:c.265A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.1813A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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ATP synthase subunit g, mitochondrial [Homo sapiens]
ATP synthase subunit g, mitochondrial [Homo sapiens]
gi|51479156|ref|NP_006467.4|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002711962	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 2, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20921021, 25186627 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002711962

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 2, 2020)

germline

clinical testing

PubMed (2)
[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 mutations in CDH1 are infrequent in women with early-onset or familial lobular breast cancers.

Schrader KA, Masciari S, Boyd N, Salamanca C, Senz J, Saunders DN, Yorida E, Maines-Bandiera S, Kaurah P, Tung N, Robson ME, Ryan PD, Olopade OI, Domchek SM, Ford J, Isaacs C, Brown P, Balmana J, Razzak AR, Miron P, Coffey K, Terry MB, et al.

J Med Genet. 2011 Jan;48(1):64-8. doi: 10.1136/jmg.2010.079814. Epub 2010 Oct 4.

PubMed [citation]

PMID:: 20921021
PMCID:: PMC3003879

Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.

Tung N, Battelli C, Allen B, Kaldate R, Bhatnagar S, Bowles K, Timms K, Garber JE, Herold C, Ellisen L, Krejdovsky J, DeLeonardis K, Sedgwick K, Soltis K, Roa B, Wenstrup RJ, Hartman AR.

Cancer. 2015 Jan 1;121(1):25-33. doi: 10.1002/cncr.29010. Epub 2014 Sep 3.

PubMed [citation]

PMID:: 25186627

Details of each submission

From Ambry Genetics, SCV002711962.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.R605G variant (also known as c.1813A>G), located in coding exon 12 of the CDH1 gene, results from an A to G substitution at nucleotide position 1813. The arginine at codon 605 is replaced by glycine, an amino acid with dissimilar properties. This alteration has been reported in an individual with lobular breast cancer diagnosed at age 42 whose family history was negative for gastric cancer (Schrader KA et al. J Med Genet, 2011 Jan;48:64-8). This alteration was also detected on a 25-gene panel test in a woman diagnosed with breast cancer before age 50 (Tung N et al. Cancer, 2015 Jan;121:25-33). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Jun 23, 2024

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