Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000542181 | SCV000628891 | pathogenic | Neuronal ceroid lipofuscinosis | 2022-11-03 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 8-9 of the CLN3 gene. This deletion is out-of-frame, and is expected to create a premature termination codon and result in an absent or disrupted protein product. Loss-of-function variants in CLN3 are known to be pathogenic (PMID: 9311735, 28542676). A similar copy number variant has been observed in individuals with juvenile neuronal ceroid lipofuscinosis, also known as Batten disease, and accounts for between 81-85% of all disease-causing alleles. (PMID: 7553855, 20187884, 21228398, 21990111, 23374165). This variant is also known as deletion of exons 7-8. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that a similar copy number variant affects CLN3 function (PMID: 10332042, 17947292, 19132115). For these reasons, this variant has been classified as Pathogenic. |