Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics Laboratory, |
RCV001199565 | SCV001162711 | pathogenic | Usher syndrome type 2 | 2020-01-09 | criteria provided, single submitter | research | |
Institute of Medical Genetics and Applied Genomics, |
RCV001268623 | SCV001447684 | likely pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Department of Otolaryngology – Head & Neck Surgery, |
RCV001375345 | SCV001572063 | likely pathogenic | Hearing impairment | 2021-04-12 | criteria provided, single submitter | clinical testing | PVS1_Strong, PM2_Moderate |
Invitae | RCV001268623 | SCV003439713 | pathogenic | not provided | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 7 of the USH1C gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in USH1C are known to be pathogenic (PMID: 10973247, 17407589, 20301442, 21203349). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with Usher syndrome (PMID: 27460420, 32531858). ClinVar contains an entry for this variant (Variation ID: 813103). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |