Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001051791 | SCV001215969 | uncertain significance | Progressive myoclonic epilepsy type 3 | 2019-03-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 84 of the KCTD7 protein (p.Arg84Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs200575329, ExAC 0.01%). This variant has not been reported in the literature in individuals with KCTD7-related conditions. 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. |
| Mendelics | RCV001051791 | SCV002516614 | pathogenic | Progressive myoclonic epilepsy type 3 | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004587027 | SCV005076074 | uncertain significance | not specified | 2024-04-26 | criteria provided, single submitter | clinical testing | Variant summary: KCTD7 c.251G>A (p.Arg84Gln) results in a conservative amino acid change located in the BTB/POZ domain (IPR000210) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251456 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.251G>A has been reported in the literature in at least one individual affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) (Metz_2018). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function. Co-immunoprecipitation assays show a reduction in binding to CUL3 (Metz_2018). The following publication has been ascertained in the context of this evaluation (PMID: 30295347). ClinVar contains an entry for this variant (Variation ID: 848103). Based on the evidence outlined above, the variant was classified as uncertain significance. |