Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000170347 | SCV002519741 | pathogenic | Developmental and epileptic encephalopathy, 30 | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000170347 | SCV004278760 | uncertain significance | Developmental and epileptic encephalopathy, 30 | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln633*) in the SIK1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SIK1 cause disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with clinical features of developmental and epileptic encephalopathy (PMID: 25839329). ClinVar contains an entry for this variant (Variation ID: 190108). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects SIK1 function (PMID: 25839329, 27966542). 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. |
OMIM | RCV000170347 | SCV000222755 | pathogenic | Developmental and epileptic encephalopathy, 30 | 2015-04-02 | no assertion criteria provided | literature only |