Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000698933 | SCV000827624 | likely pathogenic | Neuronal ceroid lipofuscinosis | 2019-04-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 112 of the CLN5 protein (p.Arg112His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs104894386, ExAC 0.006%). This variant has been observed to segregate with juvenile onset neuronal ceroid lipofuscinosis in a family (PMID: 15728307, 30078242). ClinVar contains an entry for this variant (Variation ID: 2567). Experimental studies have shown that this missense change disturbs the lysosomal trafficking of the protein (PMID: 20052765). This variant disrupts the p.Arg112 amino acid residue in CLN5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30078242). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| OMIM | RCV000002676 | SCV000022834 | pathogenic | Neuronal ceroid lipofuscinosis 5 | 2005-02-22 | no assertion criteria provided | literature only |