ClinVar Miner

Submissions for variant NM_173354.5(SIK1):c.1259C>A (p.Pro420Gln)

dbSNP: rs181611369
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000543156 SCV000656497 uncertain significance Developmental and epileptic encephalopathy, 30 2022-07-12 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SIK1 protein function. ClinVar contains an entry for this variant (Variation ID: 476079). This variant has not been reported in the literature in individuals affected with SIK1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 420 of the SIK1 protein (p.Pro420Gln).
Ambry Genetics RCV002413635 SCV002676060 uncertain significance Inborn genetic diseases 2018-03-18 criteria provided, single submitter clinical testing The p.P420Q variant (also known as c.1259C>A), located in coding exon 10 of the SIK1 gene, results from a C to A substitution at nucleotide position 1259. The proline at codon 420 is replaced by glutamine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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