ClinVar Miner

Submissions for variant NM_173354.5(SIK1):c.2012C>T (p.Pro671Leu)

gnomAD frequency: 0.00002  dbSNP: rs768025261
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001202826 SCV001373955 uncertain significance Developmental and epileptic encephalopathy, 30 2024-10-21 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 671 of the SIK1 protein (p.Pro671Leu). 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 variant has not been reported in the literature in individuals affected with SIK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 934437). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SIK1 protein function with a negative predictive value of 95%. 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.
Baylor Genetics RCV001202826 SCV001523982 uncertain significance Developmental and epileptic encephalopathy, 30 2019-08-22 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV004671247 SCV005166498 uncertain significance Inborn genetic diseases 2024-03-26 criteria provided, single submitter clinical testing The c.2012C>T (p.P671L) alteration is located in exon 14 (coding exon 13) of the SIK1 gene. This alteration results from a C to T substitution at nucleotide position 2012, causing the proline (P) at amino acid position 671 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.