NM_022124.6(CDH23):c.8803C>T (p.Arg2935Ter) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 15, 2025
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:: RCV000760396.12

Allele description [Variation Report for NM_022124.6(CDH23):c.8803C>T (p.Arg2935Ter)]

NM_022124.6(CDH23):c.8803C>T (p.Arg2935Ter)

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.8803C>T (p.Arg2935Ter)

HGVS:

NC_000010.11:g.71809900C>T
NG_008835.1:g.417954C>T
NM_001171933.1:c.2083C>T
NM_001171934.1:c.2083C>T
NM_022124.6:c.8803C>TMANE SELECT
NP_001165404.1:p.Arg695Ter
NP_001165405.1:p.Arg695Ter
NP_071407.4:p.Arg2935Ter
NC_000010.10:g.73569657C>T
NM_022124.5:c.8803C>T

Protein change:

R2935*

Links:

dbSNP: rs1190307769

NCBI 1000 Genomes Browser:

rs1190307769

Molecular consequence:

NM_001171933.1:c.2083C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001171934.1:c.2083C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_022124.6:c.8803C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000890269	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 17, 2024)	germline	clinical testing	Citation Link,
SCV002016988	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002242999	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 15, 2025)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11138009, 21940737, 25211151, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000890269

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(May 17, 2024)

germline

clinical testing

Citation Link,

SCV002016988

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 15, 2021)

germline

clinical testing

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

SCV002242999

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 15, 2025)

germline

clinical testing

PubMed (4)
[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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D.

Bolz H, von Brederlow B, Ramírez A, Bryda EC, Kutsche K, Nothwang HG, Seeliger M, del C-Salcedó Cabrera M, Vila MC, Molina OP, Gal A, Kubisch C.

Nat Genet. 2001 Jan;27(1):108-12.

PubMed [citation]

PMID:: 11138009

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000890269.2

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

Description

Identified in patients with bilateral sensorineural hearing loss referred for genetic testing at GeneDx and in published literature; patients were younger than the expected age of onset for visual symptoms of Usher syndrome (PMID: 35020051); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21689626, 11750125, 25211151, 35020051)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002016988.4

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

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002242999.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Arg2935*) in the CDH23 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDH23 are known to be pathogenic (PMID: 11138009, 21940737). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 25211151). ClinVar contains an entry for this variant (Variation ID: 620124). For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 25, 2025

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