Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000187112 | SCV000240687 | uncertain significance | not provided | 2017-06-21 | criteria provided, single submitter | clinical testing | p.Ala22Thr (GCC>ACC): c.64 G>A in exon 1 of the CLN6 gene (NM_017882.2). The Ala22Thr missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. Ala22Thr alters a position that is not conserved in the signal peptide domain of the CLN6 protein and several in-silico algorithms predict it may be benign. However, other missense mutations in this region of the protein have been reported in association with late-infantile neuronal ceroid lipofuscinosis (NCL) and the amino acid substitution is non-conservative as a non-polar Alanine residue is replaced by a polar Threonine residue. Therefore, based on the currently available information, it is unclear whether Ala22Thr is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
Invitae | RCV000813039 | SCV000953372 | uncertain significance | Neuronal ceroid lipofuscinosis | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 22 of the CLN6 protein (p.Ala22Thr). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CLN6-related conditions. ClinVar contains an entry for this variant (Variation ID: 205181). 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 tolerated. 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. |