Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000536953 | SCV000656502 | likely benign | Developmental and epileptic encephalopathy, 30 | 2024-10-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002316585 | SCV000851588 | likely benign | Inborn genetic diseases | 2023-04-11 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV005239217 | SCV005884612 | uncertain significance | not specified | 2024-12-10 | criteria provided, single submitter | clinical testing | Variant summary: SIK1 c.1463-5C>T 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. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 7.5e-05 in 239872 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in SIK1 causing Developmental And Epileptic Encephalopathy, 30, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1463-5C>T in individuals affected with Developmental And Epileptic Encephalopathy, 30 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 476083). Based on the evidence outlined above, the variant was classified as uncertain significance. |