ClinVar Miner

Submissions for variant NM_173354.5(SIK1):c.1904C>T (p.Pro635Leu)

dbSNP: rs779904079
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001331845 SCV001523981 uncertain significance Developmental and epileptic encephalopathy, 30 2019-08-01 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV001331845 SCV001531377 uncertain significance Developmental and epileptic encephalopathy, 30 2023-12-21 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 635 of the SIK1 protein (p.Pro635Leu). This variant is present in population databases (rs779904079, gnomAD 0.005%). 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: 1030318). 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 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.
Ambry Genetics RCV002546511 SCV003703224 uncertain significance Inborn genetic diseases 2021-07-09 criteria provided, single submitter clinical testing The c.1904C>T (p.P635L) alteration is located in exon 13 (coding exon 12) of the SIK1 gene. This alteration results from a C to T substitution at nucleotide position 1904, causing the proline (P) at amino acid position 635 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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