Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000477605 | SCV000549229 | pathogenic | Neuronal ceroid lipofuscinosis | 2024-01-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.His315Glnfs*67) 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). This variant is present in population databases (rs386833740, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with juvenile neuronal ceroid lipofuscinoses (PMID: 9311735, 23374165). ClinVar contains an entry for this variant (Variation ID: 56292). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000049704 | SCV000917247 | pathogenic | Neuronal ceroid lipofuscinosis 3 | 2017-11-13 | criteria provided, single submitter | clinical testing | Variant summary: The CLN3 c.944dupA (p.His315GlufsX67) variant results in a premature termination codon, predicted to cause a truncated or absent CLN3 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/245564 control chromosomes (gnomAD) at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic CLN3 variant (0.0006124). The variant has been reported in affected individuals in the literature (Munroe_1997, Santorelli_2013, Kwon_2011). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. Taken together, this variant is classified as pathogenic. |
| Baylor Genetics | RCV000049704 | SCV004214317 | pathogenic | Neuronal ceroid lipofuscinosis 3 | 2023-09-03 | criteria provided, single submitter | clinical testing | |
| Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000049704 | SCV000082111 | probable-pathogenic | Neuronal ceroid lipofuscinosis 3 | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. | |
| Counsyl | RCV000049704 | SCV001132154 | pathogenic | Neuronal ceroid lipofuscinosis 3 | 2018-01-10 | no assertion criteria provided | clinical testing |