Submissions for variant NM_022124.6(CDH23):c.9860G>A (p.Gly3287Asp) (rs562590210)

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV000313005	SCV000363953	uncertain significance	CDH23-Related Disorders	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000367632	SCV000363954	uncertain significance	Nonsyndromic Hearing Loss, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000263857	SCV000363955	uncertain significance	Retinitis pigmentosa-deafness syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000406507	SCV000483111	likely benign	Galactosylceramide beta-galactosidase deficiency	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000298268	SCV000483112	likely benign	Atypical Gaucher Disease	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000350786	SCV000483113	likely benign	Metachromatic leukodystrophy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000404504	SCV000483114	likely benign	Combined saposin deficiency	2016-06-14	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000612885	SCV000731723	uncertain significance	not specified	2017-06-26	criteria provided, single submitter	clinical testing	The p.Gly3287Asp variant in CDH23 has not been previously reported in individual s with hearing loss. It has been reported in ClinVar (Variation ID 300477) with conflicting interpretations. It has also been identified in 0.1% (12/17020) East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.bro adinstitute.org; dbSNP rs562590210). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic ro le. Computational prediction tools and conservation analyses do not provide stro ng support for or against an impact to the protein. In summary, the clinical sig nificance of the p.Gly3287Asp variant is uncertain.
Illumina Clinical Services Laboratory,Illumina	RCV001105176	SCV001262100	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 Clinical Services Laboratory,Illumina	RCV001105177	SCV001262101	uncertain significance	Deafness, autosomal recessive 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.