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NM_004360.5(CDH1):c.1840A>G (p.Ile614Val) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jun 23, 2022
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:
RCV000132427.8

Allele description [Variation Report for NM_004360.5(CDH1):c.1840A>G (p.Ile614Val)]

NM_004360.5(CDH1):c.1840A>G (p.Ile614Val)

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.1840A>G (p.Ile614Val)
HGVS:
  • NC_000016.10:g.68822129A>G
  • NG_008021.1:g.89838A>G
  • NM_001317184.2:c.1657A>G
  • NM_001317185.2:c.292A>G
  • NM_001317186.2:c.-126A>G
  • NM_004360.5:c.1840A>GMANE SELECT
  • NP_001304113.1:p.Ile553Val
  • NP_001304114.1:p.Ile98Val
  • NP_004351.1:p.Ile614Val
  • LRG_301t1:c.1840A>G
  • LRG_301:g.89838A>G
  • NC_000016.9:g.68856032A>G
  • NM_004360.3:c.1840A>G
  • NM_004360.4:c.1840A>G
  • p.I614V
Protein change:
I553V
Links:
dbSNP: rs587782838
NCBI 1000 Genomes Browser:
rs587782838
Molecular consequence:
  • NM_001317186.2:c.-126A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001317184.2:c.1657A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317185.2:c.292A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004360.5:c.1840A>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000187520Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Jun 23, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV001343678Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Sep 15, 2021) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Prevalence of deleterious mutations among patients with breast cancer referred for multigene panel testing in a Romanian population.

Goidescu IG, Caracostea G, Eniu DT, Stamatian FV.

Clujul Med. 2018;91(2):157-165. doi: 10.15386/cjmed-894. Epub 2018 Apr 25.

PubMed [citation]
PMID:
29785153
PMCID:
PMC5958980

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Ambry Genetics, SCV000187520.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The p.I614V variant (also known as c.1840A>G), located in coding exon 12 of the CDH1 gene, results from an A to G substitution at nucleotide position 1840. The isoleucine at codon 614 is replaced by valine, an amino acid with highly similar properties. This alteration was reported in 1/130 consecutive breast cancer cases meeting NCCN criteria for genetic testing and was classified as a VUS (Goidescu IG et al. Clujul Med. 2018 Apr;91:157-165). This amino acid position is highly 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV001343678.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This missense variant replaces isoleucine with valine at codon 614 of the CDH1 protein. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 29785153). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024