Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000674211 | SCV000799511 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 | 2018-04-25 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001385690 | SCV001585639 | pathogenic | not provided | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 30 of the MYO7A 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 MYO7A are known to be pathogenic (PMID: 8900236, 25404053). 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. Disruption of this splice site has been observed in individual(s) with Usher syndrome (PMID: 27729122). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 558000). 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. |