Submissions for variant NM_022124.6(CDH23):c.4747G>T (p.Gly1583Cys)

dbSNP: rs775013186

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001202914	SCV001374049	uncertain significance	not provided	2024-08-19	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 1583 of the CDH23 protein (p.Gly1583Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 934509). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CDH23 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics	RCV001331232	SCV001523226	uncertain significance	Autosomal recessive nonsyndromic hearing loss 12	2019-05-10	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV001202914	SCV002817456	uncertain significance	not provided	2022-06-27	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002561108	SCV003601590	uncertain significance	Inborn genetic diseases	2022-01-04	criteria provided, single submitter	clinical testing	The c.4747G>T (p.G1583C) alteration is located in exon 38 (coding exon 37) of the CDH23 gene. This alteration results from a G to T substitution at nucleotide position 4747, causing the glycine (G) at amino acid position 1583 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.