Submissions for variant NM_022124.6(CDH23):c.9670C>T (p.Arg3224Trp)

gnomAD frequency: 0.00106  dbSNP: rs111033457

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039315	SCV000062999	uncertain significance	not specified	2018-10-10	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Arg3224Trp va riant in CDH23 has been identified by our laboratory in 2 individuals with heari ng loss; however, it did not segregate with disease in an affected sibling. This variant has also been identified in 0.18% (132/72638) of European chromosomes, including 1 homozygote, by gnomAD (http://gnomad.broadinstitute.org). This varia nt has also been reported in ClinVar (Variation ID 46078). Computational predict ion tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of the p. Arg3224Trp variant is uncertain, these data suggest that it is more likely to be benign. ACMG/AMP Criteria applied: BS1_Supporting.
Eurofins Ntd Llc (ga)	RCV000725356	SCV000336272	uncertain significance	not provided	2015-10-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000286542	SCV000363944	uncertain significance	Autosomal recessive nonsyndromic hearing loss 12	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000341398	SCV000363945	uncertain significance	Usher syndrome type 1D	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV004528199	SCV000363946	uncertain significance	CDH23-related disorder	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000725356	SCV001414858	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000039315	SCV001475763	benign	not specified	2019-11-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000725356	SCV001983811	uncertain significance	not provided	2021-05-04	criteria provided, single submitter	clinical testing	Observed in unrelated patients with idiopathic posterior uveitis and POHS in published literature (Li et al., 2021); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32707200)
Natera, Inc.	RCV001272665	SCV001454904	uncertain significance	Usher syndrome type 1	2020-04-17	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000725356	SCV001798918	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000725356	SCV001956349	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000725356	SCV001970417	uncertain significance	not provided		no assertion criteria provided	clinical testing