Submissions for variant NM_022124.6(CDH23):c.4405A>G (p.Ile1469Val)

gnomAD frequency: 0.00014  dbSNP: rs200635365

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000156528	SCV000206247	uncertain significance	not specified	2014-05-23	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Ile1469Val vari ant in CDH23 has not been previously reported in individuals with hearing loss b ut has been reported in the dbSNP database without frequency information (dbSNP rs200635365). Computational prediction tools and conservation analyses suggest t hat the Ile1469Val variant may not impact the protein, though this information i s not predictive enough to rule out pathogenicity. In summary, while the clinica l significance of the Ile1469Val variant is uncertain, the computational data su ggests that it is more likely to be benign.
GeneDx	RCV000766640	SCV000570418	uncertain significance	not provided	2020-10-09	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26969326)
Illumina Laboratory Services, Illumina	RCV000778901	SCV000915308	uncertain significance	Autosomal recessive nonsyndromic hearing loss 12	2017-08-08	criteria provided, single submitter	clinical testing	The CDH23 gene is one of at least 37 genes in which variants are known to cause autosomal recessive nonsyndromic hearing loss. The CDH23 c.4405A>G (p.Ile1469Val) missense variant has been reported in one study in which it is found in a compound heterozygous state with an intron variant in one patient with autosomal recessive nonsyndromic hearing loss (Sloan-Heggen et al. 2016). Control data are not available for this variant which is reported at a frequency of 0.00157 in the South Asian population from the Exome Aggregation Consortium. The evidence for this variant is limited, therefore the p.Ile1469Val variant is considered a variant of unknown but suspicious for pathogenicity for autosomal recessive nonsyndromic hearing loss. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae	RCV000766640	SCV001225964	likely benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001106863	SCV001263972	uncertain significance	Usher syndrome type 1D	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Baylor Genetics	RCV000778901	SCV001523225	uncertain significance	Autosomal recessive nonsyndromic hearing loss 12	2020-02-18	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Fulgent Genetics, Fulgent Genetics	RCV002492595	SCV002794412	uncertain significance	Autosomal recessive nonsyndromic hearing loss 12; Usher syndrome type 1D; Pituitary adenoma 5, multiple types	2021-09-09	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003474814	SCV004212355	uncertain significance	Pituitary adenoma 5, multiple types	2022-09-26	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000766640	SCV001921250	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000766640	SCV001955716	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000766640	SCV001967171	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001835699	SCV002087390	uncertain significance	Usher syndrome type 1	2020-01-16	no assertion criteria provided	clinical testing