Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000187102 | SCV000240677 | uncertain significance | not provided | 2013-10-16 | criteria provided, single submitter | clinical testing | p.Phe236Val (TTC>GTC): c.706 T>G in exon 7 of the CLN6 gene (NM_017882.2). The Phe236Val missense change has not been published as a mutation, nor has it been reported as a benign polymorphism 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. This variant is a conservative substitution of one uncharged, non-polar amino acid for another; however, it alters a conserved position in the sixth transmembrane domain, and other missense mutations associated with neuronal ceroid lipofuscinosis have been reported in this region of the protein (Phe234Leu and Met241Thr). In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether Phe236Val is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
Invitae | RCV000702414 | SCV000831267 | uncertain significance | Neuronal ceroid lipofuscinosis | 2022-06-20 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CLN6-related conditions. This variant is present in population databases (rs796052358, gnomAD 0.0009%). This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 236 of the CLN6 protein (p.Phe236Val). ClinVar contains an entry for this variant (Variation ID: 205173). 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |