Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV000049958 | SCV004214370 | likely pathogenic | Neuronal ceroid lipofuscinosis 5 | 2023-10-11 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003531948 | SCV004296505 | likely pathogenic | Neuronal ceroid lipofuscinosis | 2023-06-14 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 258 of the CLN5 protein (p.Tyr258Asp). 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. 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 expected to disrupt CLN5 protein function. ClinVar contains an entry for this variant (Variation ID: 56545). This missense change has been observed in individuals with autosomal recessive neuronal ceroid lipofuscinosis (PMID: 17607606, 28542837). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). |
Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000049958 | SCV000082367 | probable-pathogenic | Neuronal ceroid lipofuscinosis 5 | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |