Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
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. |
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, |
RCV001241939 | SCV003831039 | uncertain significance | not provided | 2021-11-30 | criteria provided, single submitter | clinical testing | |
Gene |
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 |