Submissions for variant NM_022124.6(CDH23):c.2711C>T (p.Pro904Leu)

gnomAD frequency: 0.00021  dbSNP: rs199894395

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000221903	SCV000270033	likely benign	not specified	2015-07-17	criteria provided, single submitter	clinical testing	p.Pro904Leu in exon 24 of CDH23: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, 3 mammals (opossum, Tasmanian devil, wallaby) carry a leucine (Leu) at thi s position. In addition, computational prediction tools do not suggest a high li kelihood of impact to the protein. It has also been identified in 0.1% (40/66558 ) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org; dbSNP rs199894395).
Illumina Laboratory Services, Illumina	RCV000403602	SCV000363657	uncertain significance	Autosomal recessive nonsyndromic hearing loss 12	2018-01-13	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	RCV000309502	SCV000363658	uncertain significance	Usher syndrome type 1D	2018-01-13	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	RCV000345859	SCV000363659	uncertain significance	CDH23-Related Disorders	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV001245326	SCV001418608	likely benign	not provided	2024-01-17	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001245326	SCV002011392	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002519603	SCV003726188	uncertain significance	Inborn genetic diseases	2022-12-21	criteria provided, single submitter	clinical testing	The c.2711C>T (p.P904L) alteration is located in exon 24 (coding exon 23) of the CDH23 gene. This alteration results from a C to T substitution at nucleotide position 2711, causing the proline (P) at amino acid position 904 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV001245326	SCV003923784	uncertain significance	not provided	2022-11-07	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
CeGaT Center for Human Genetics Tuebingen	RCV001245326	SCV004126724	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	CDH23: BP4
Natera, Inc.	RCV001275944	SCV001461624	uncertain significance	Usher syndrome type 1	2020-04-15	no assertion criteria provided	clinical testing