Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001039257 | SCV001202780 | uncertain significance | Neuronal ceroid lipofuscinosis | 2019-03-28 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with tyrosine at codon 126 of the CLN5 protein (p.Cys126Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with neuronal ceroid lipofuscinosis (PMID: 19383612, 20157158). ClinVar contains an entry for this variant (Variation ID: 2569). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
| OMIM | RCV000002678 | SCV000022836 | pathogenic | Neuronal ceroid lipofuscinosis 5 | 2010-02-16 | no assertion criteria provided | literature only |