Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000049692 | SCV000793644 | likely pathogenic | Neuronal ceroid lipofuscinosis 3 | 2017-08-22 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001853044 | SCV002239644 | pathogenic | Neuronal ceroid lipofuscinosis | 2023-04-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 56280). This variant is also known as c.558delAG. This premature translational stop signal has been observed in individual(s) with clinical features of neuronal ceroid lipofuscinosis (PMID: 9311735). This variant is present in population databases (rs386833729, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gly187Aspfs*48) in the CLN3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLN3 are known to be pathogenic (PMID: 9311735, 28542676). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001853044 | SCV002548121 | likely pathogenic | Neuronal ceroid lipofuscinosis | 2022-05-31 | criteria provided, single submitter | clinical testing | Variant summary: CLN3 c.558_559delAG (p.Gly187AspfsX48) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 247310 control chromosomes. c.558_559delAG has been reported in the literature in an individual with early onset retinitis pigmentosa and an individual affected with Juvenile Neuronal Ceroid-Lipofuscinosis (Juvenile Batten Disease)(Di Iorio_2017, Munroe_1997). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic and the other as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000049692 | SCV000082099 | probable-pathogenic | Neuronal ceroid lipofuscinosis 3 | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |