NM_022124.6(CDH23):c.9569C>T (p.Ala3190Val) AND CDH23-related disorder

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 5, 2017
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:: RCV004528198.2

Allele description [Variation Report for NM_022124.6(CDH23):c.9569C>T (p.Ala3190Val)]

NM_022124.6(CDH23):c.9569C>T (p.Ala3190Val)

Gene:

CDH23:cadherin related 23 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q22.1

Genomic location:

Preferred name:

NM_022124.6(CDH23):c.9569C>T (p.Ala3190Val)

HGVS:

NC_000010.11:g.71812826C>T
NG_008835.1:g.420880C>T
NM_001171933.1:c.2849C>T
NM_001171934.1:c.2849C>T
NM_001171935.1:c.260C>T
NM_001171936.1:c.260C>T
NM_022124.6:c.9569C>TMANE SELECT
NP_001165404.1:p.Ala950Val
NP_001165405.1:p.Ala950Val
NP_001165406.1:p.Ala87Val
NP_001165407.1:p.Ala87Val
NP_071407.4:p.Ala3190Val
NC_000010.10:g.73572583C>T
NM_022124.5:c.9569C>T
NM_022124.6(CDH23):c.9569C>TMANE SELECT
c.9569C>T

Protein change:

A3190V

Links:

dbSNP: rs111033536

NCBI 1000 Genomes Browser:

rs111033536

Molecular consequence:

NM_001171933.1:c.2849C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001171934.1:c.2849C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001171935.1:c.260C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001171936.1:c.260C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_022124.6:c.9569C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: CDH23-related disorder
Synonyms:: CDH23-related condition; CDH23-Related Disorders
Identifiers:

Recent activity

Clear Turn Off Turn On

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
SCV000915480	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Uncertain significance (Dec 5, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27068579, 25404053 Citation Link,
SCV005366710	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Uncertain significance (Sep 12, 2024)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000915480

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Uncertain significance
(Dec 5, 2017)

germline

clinical testing

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

Citation Link,

SCV005366710

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Uncertain significance
(Sep 12, 2024)

germline

clinical testing

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

DNA Diagnostics of Hereditary Hearing Loss: A Targeted Resequencing Approach Combined with a Mutation Classification System.

Sommen M, Schrauwen I, Vandeweyer G, Boeckx N, Corneveaux JJ, van den Ende J, Boudewyns A, De Leenheer E, Janssens S, Claes K, Verstreken M, Strenzke N, Predöhl F, Wuyts W, Mortier G, Bitner-Glindzicz M, Moser T, Coucke P, Huentelman MJ, Van Camp G.

Hum Mutat. 2016 Aug;37(8):812-9. doi: 10.1002/humu.22999. Epub 2016 May 6.

PubMed [citation]

PMID:: 27068579

Targeted next generation sequencing for molecular diagnosis of Usher syndrome.

Aparisi MJ, Aller E, Fuster-García C, García-García G, Rodrigo R, Vázquez-Manrique RP, Blanco-Kelly F, Ayuso C, Roux AF, Jaijo T, Millán JM.

Orphanet J Rare Dis. 2014 Nov 18;9:168. doi: 10.1186/s13023-014-0168-7.

PubMed [citation]

PMID:: 25404053
PMCID:: PMC4245769

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000915480.1

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

Description

The CDH23 c.9569C>T (p.Ala3190Val) missense variant has been reported in two studies in which it is identified in a compound heterozygous state in two individuals, one with a diagnosis of Usher syndrome and one with autosomal recessive nonsyndromic hearing loss (Aparisi et al. 2014; Sommen et al. 2016). Control data are unavailable for this variant, which is reported at a frequency of 0.00047 in the European (non-Finnish) population of the Exome Aggregation Consortium. The evidence for this variant is limited. Based on the evidence, the p.Ala3190Val variant is classified as a variant of unknown significance but suspicious for pathogenicity for CDH23-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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

From PreventionGenetics, part of Exact Sciences, SCV005366710.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The CDH23 c.9569C>T variant is predicted to result in the amino acid substitution p.Ala3190Val. This variant has been reported in the presumed compound heterozygous state with a duplication of exon 29 (that was not confirmed by orthogonal method) in an individual with Usher syndrome (Aparisi et al. 2014. PubMed ID: 25404053). It has also been reported together with another variant of uncertain significance in CDH23 in patient with hearing loss (Table S2, Sommen et al. 2016. PubMed ID: 27068579) and in the heterozygous state without a second disease-causing variant in another individual with non-syndromic hearing loss (NSHL) (Table A2, Clabout et al. 2022. PubMed ID: 36672845). Of note, this variant has also been observed in the homozygous state in a patient tested for Usher syndrome at PreventionGenetics who was also homozygous for a protein-truncating variant in the PCDH15 gene (internal data). This variant is reported in 0.068% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

#	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 24, 2024

ClinVar

Relating variation to medicine