Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000431143 | SCV000523128 | likely benign | not specified | 2016-01-20 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Labcorp Genetics |
RCV002062553 | SCV002352593 | likely benign | Benign neonatal seizures | 2023-11-27 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000431143 | SCV002819356 | uncertain significance | not specified | 2022-12-08 | criteria provided, single submitter | clinical testing | Variant summary: KCNQ3 c.1800-12G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant weakens a canonical 3' acceptor site, whereas two predict the variant has no significant impact on splicing. These predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251274 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1800-12G>A in individuals affected with Benign Familial Neonatal Seizures and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and both laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |