Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000187092 | SCV000240667 | pathogenic | not provided | 2012-06-19 | criteria provided, single submitter | clinical testing | IVS3+1 G>A: c.297+1 G>A in intron 3 of the CLN6 gene (NM_017882.2). The c.297+1 G>A splice site mutation in the CLN6 gene destroys the canonical splice donor site in intron 3. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Although this mutation has not been previously reported to our knowledge, it is considered a disease-causing mutation. The variant is found in INFANT-EPI panel(s). |
Invitae | RCV002513990 | SCV002977290 | likely pathogenic | Neuronal ceroid lipofuscinosis | 2021-12-29 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 205164). This variant has not been reported in the literature in individuals affected with CLN6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 of the CLN6 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 CLN6 are known to be pathogenic (PMID: 19135028). |