NM_004360.5(CDH1):c.1703C>G (p.Thr568Arg) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 19, 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:: RCV001326496.8

Allele description [Variation Report for NM_004360.5(CDH1):c.1703C>G (p.Thr568Arg)]

NM_004360.5(CDH1):c.1703C>G (p.Thr568Arg)

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.1703C>G (p.Thr568Arg)

Other names:

NM_004360.5(CDH1):c.1703C>G; p.Thr568Arg

HGVS:

NC_000016.10:g.68819417C>G
NG_008021.1:g.87126C>G
NM_001317184.2:c.1520C>G
NM_001317185.2:c.155C>G
NM_001317186.2:c.-254-2584C>G
NM_004360.5:c.1703C>GMANE SELECT
NP_001304113.1:p.Thr507Arg
NP_001304114.1:p.Thr52Arg
NP_004351.1:p.Thr568Arg
LRG_301t1:c.1703C>G
LRG_301:g.87126C>G
NC_000016.9:g.68853320C>G
NM_004360.3:c.1703C>G

Protein change:

T507R

Links:

dbSNP: rs786202712

NCBI 1000 Genomes Browser:

rs786202712

Molecular consequence:

NM_001317186.2:c.-254-2584C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001317184.2:c.1520C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001317185.2:c.155C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.1703C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary diffuse gastric adenocarcinoma (HDGC)
Synonyms:: Hereditary diffuse gastric cancer
Identifiers:: MONDO: MONDO:0007648; MedGen: C1708349; Orphanet: 26106; OMIM: 137215

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ST8SIA4 [Pantherophis guttatus]
ST8SIA4 [Pantherophis guttatus]
Gene ID:117679094

Gene
Schizophrenia 5
Schizophrenia 5

MedGen
FBXO46 F-box protein 46 [Homo sapiens]
FBXO46 F-box protein 46 [Homo sapiens]
Gene ID:23403

Gene
Gene Links for GEO Profiles (Select 44331593) (1)
Gene
Assembly for Nucleotide (Select 2738408810) (1)
Assembly

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001517528	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 19, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31642931, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001517528

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 19, 2022)

germline

clinical testing

PubMed (2)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Assessment of Diagnostic Outcomes of RNA Genetic Testing for Hereditary Cancer.

Karam R, Conner B, LaDuca H, McGoldrick K, Krempely K, Richardson ME, Zimmermann H, Gutierrez S, Reineke P, Hoang L, Allen K, Yussuf A, Farber-Katz S, Rana HQ, Culver S, Lee J, Nashed S, Toppmeyer D, Collins D, Haynes G, Pesaran T, Dolinsky JS, et al.

JAMA Netw Open. 2019 Oct 2;2(10):e1913900. doi: 10.1001/jamanetworkopen.2019.13900.

PubMed [citation]

PMID:: 31642931
PMCID:: PMC6820040

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001517528.4

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 428619). This missense change has been observed in individual(s) with diffuse gastric cancer (PMID: 31642931). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 568 of the CDH1 protein (p.Thr568Arg).

#	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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