Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000265935 | SCV000363726 | uncertain significance | Usher syndrome type 1D | 2017-04-28 | 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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV000300732 | SCV000363727 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 12 | 2017-04-28 | criteria provided, single submitter | clinical testing | The CDH23 c.4103C>T (p.Thr1368Met) missense variant has been reported in one study in which it was found in a compound heterozygous state in one individual with hearing loss (Miyagawa et al. 2012). The p.Thr1368Met variant was absent from 192 control individuals with normal hearing and is reported at a frequency of 0.00109 in the East Asian population of the Exome Aggregation Consortium, but this is based on only one allele. The evidence for this variant is limited. The p.Thr1368Met variant is therefore classified as a variant of unknown significance, but suspicious for pathogenicity for nonsyndromic hearing loss. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV002520615 | SCV003521492 | uncertain significance | not provided | 2022-05-21 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1368 of the CDH23 protein (p.Thr1368Met). This variant is present in population databases (rs762247872, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of CDH23-related conditions (PMID: 22899989). ClinVar contains an entry for this variant (Variation ID: 300429). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C65"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |