ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.290T>C (p.Leu97Pro)

dbSNP: rs1925418549
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel RCV003235465 SCV003933680 likely pathogenic CDKL5 disorder 2023-04-14 reviewed by expert panel curation The p.Leu97Pro variant in CDKL5 occurs in the de novo state (biological parentage confirmed) in an individual (GeneDx Internal Database) (PS2). The p.Leu97Pro variant in CDKL5 is absent from gnomAD (PM2_supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, the p.Leu97Pro variant in CDKL5 is classified as likely pathogenic for a CDKL5-related disorder based on the ACMG/AMP criteria (PS2, PM2_supporting, PP3).
Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics RCV001089706 SCV001245190 likely pathogenic Developmental and epileptic encephalopathy, 2 2020-02-14 criteria provided, single submitter clinical testing
Invitae RCV001301919 SCV001491104 pathogenic Developmental and epileptic encephalopathy, 2; Angelman syndrome-like 2021-04-15 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt CDKL5 protein function. This variant has been observed in individual(s) with clinical features of CDKL5-related conditions (Invitae, external communication). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 870171). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 97 of the CDKL5 protein (p.Leu97Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline.

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