Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000483654 | SCV000571671 | uncertain significance | not provided | 2016-09-13 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CLN5 gene. The R339I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R339I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV000814083 | SCV000954480 | uncertain significance | Neuronal ceroid lipofuscinosis | 2022-07-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 339 of the CLN5 protein (p.Arg339Ile). This variant is present in population databases (rs770688728, gnomAD 0.006%). 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: 422251). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |
Genome- |
RCV001785630 | SCV002027075 | uncertain significance | Neuronal ceroid lipofuscinosis 5 | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000814083 | SCV002087981 | uncertain significance | Neuronal ceroid lipofuscinosis | 2020-08-28 | no assertion criteria provided | clinical testing |