ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.4762C>T (p.Arg1588Trp)

dbSNP: rs137937502
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001103916 SCV001260729 uncertain significance Autosomal recessive nonsyndromic hearing loss 12 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001103917 SCV001260730 likely benign 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae RCV001241939 SCV001414995 likely pathogenic not provided 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1588 of the CDH23 protein (p.Arg1588Trp). This variant is present in population databases (rs137937502, gnomAD 0.1%). This missense change has been observed in individuals with CDH23-related conditions (PMID: 23967202, 25587757, 26346818, 27792758, 30123251, 30828794, 31872526, 34416374, 34824372, 35020051). ClinVar contains an entry for this variant (Variation ID: 877825). Advanced 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 at Invitae 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
3billion RCV001103916 SCV002059032 uncertain significance Autosomal recessive nonsyndromic hearing loss 12 2022-01-03 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000180, PM2_M). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.
Revvity Omics, Revvity RCV001241939 SCV003831039 uncertain significance not provided 2021-11-30 criteria provided, single submitter clinical testing
GeneDx RCV001241939 SCV004023458 uncertain significance not provided 2023-03-21 criteria provided, single submitter clinical testing Reported in the homozygous state in patients with hearing loss as well as a relative with normal hearing (Miyagawa et al., 2012); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34416374, 31872526, 23967202, 30828794, 28265457, 26346818, 25587757, 26763877, 17850630, 27792758, 24767429, 30123251, 34426522, 34403091, 33297549, 34599366, 34824372, 35020051, 36468022, 22899989)
Baylor Genetics RCV003473716 SCV004210586 likely pathogenic Pituitary adenoma 5, multiple types 2023-10-26 criteria provided, single submitter clinical testing

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