Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001385144 | SCV001584902 | pathogenic | Neuronal ceroid lipofuscinosis | 2023-08-18 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CLN6 protein function. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1072427). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 256 of the CLN6 protein (p.Asp256Glu). This variant is present in population databases (rs760271120, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of neuronal ceroid lipofuscinosis (PMID: 22883287, 24102492). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. |
| Gene |
RCV001560278 | SCV001782655 | likely pathogenic | not provided | 2023-10-10 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22883287, 24102492, 30561534, 3052888, 37802651, 35505348) |