Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000673013 | SCV000798177 | uncertain significance | Usher syndrome type 1C; Autosomal recessive nonsyndromic hearing loss 18A | 2018-02-27 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002531327 | SCV003296986 | uncertain significance | not provided | 2022-07-05 | criteria provided, single submitter | clinical testing | The USH1C gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_153676.3, and corresponds to NM_005709.3:c.1284+6878_1284+6881delins21 in the primary transcript. This sequence change affects an acceptor splice site in intron 16 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), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in USH1C cause disease. This variant is present in population databases (rs769675063, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with USH1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 556943). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. |