Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000820427 | SCV000961139 | uncertain significance | Neuronal ceroid lipofuscinosis | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 399 of the CLN5 protein (p.Ile399Val). This variant is present in population databases (rs762333226, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CLN5-related conditions. ClinVar contains an entry for this variant (Variation ID: 662712). 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 CLN5 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV001546138 | SCV001765605 | uncertain significance | not provided | 2023-08-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously reported as pathogenic or benign to our knowledge |
Genome- |
RCV001275306 | SCV002027080 | uncertain significance | Neuronal ceroid lipofuscinosis 5 | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002537470 | SCV003694382 | uncertain significance | Inborn genetic diseases | 2022-08-03 | criteria provided, single submitter | clinical testing | The c.1195A>G (p.I399V) alteration is located in exon 4 (coding exon 4) of the CLN5 gene. This alteration results from a A to G substitution at nucleotide position 1195, causing the isoleucine (I) at amino acid position 399 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001275306 | SCV001460328 | uncertain significance | Neuronal ceroid lipofuscinosis 5 | 2020-04-16 | no assertion criteria provided | clinical testing |