Submissions for variant NM_022124.6(CDH23):c.8444G>A (p.Arg2815His)

gnomAD frequency: 0.00004  dbSNP: rs376835293

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000827303	SCV000968940	likely benign	not provided	2018-06-05	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000827303	SCV001090828	benign	not provided	2024-10-07	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001102967	SCV001259668	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	RCV001102968	SCV001259669	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.
Genome-Nilou Lab	RCV001102967	SCV001781358	uncertain significance	Autosomal recessive nonsyndromic hearing loss 12	2021-07-14	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001102968	SCV001781359	uncertain significance	Usher syndrome type 1D	2021-07-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002536093	SCV003734878	uncertain significance	Inborn genetic diseases	2022-06-27	criteria provided, single submitter	clinical testing	The c.8444G>A (p.R2815H) alteration is located in exon 59 (coding exon 58) of the CDH23 gene. This alteration results from a G to A substitution at nucleotide position 8444, causing the arginine (R) at amino acid position 2815 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc.	RCV001276055	SCV001461883	likely benign	Usher syndrome type 1	2020-04-17	no assertion criteria provided	clinical testing