Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002281041 | SCV002569928 | uncertain significance | CDKL5 disorder | 2022-08-25 | reviewed by expert panel | curation | The p.Cys291Tyr variant in CDKL5 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with severe early-onset encephalopathy (PMID 18809835) (PM6). The p.Cys291Tyr variant in CDKL5 is absent from gnomAD (PM2_Supporting). The p.Cys291Tyr variant has been observed in at least 1 other individual with CDKL5-related disorder (PMID 18809835, PMID 25657822) (PS4_Supporting). In summary, the p.Cys291Tyr variant in CDKL5 is classified as a variant of unknown significance based on the ACMG/AMP criteria (PM6, PM2_Supporting, PS4_Supporting). |
Invitae | RCV001203327 | SCV001374486 | uncertain significance | Developmental and epileptic encephalopathy, 2; Angelman syndrome-like | 2022-08-15 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 11505). This missense change has been observed in individual(s) with clinical features of CDKL5-related disorder (PMID: 18809835, 25657822). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 291 of the CDKL5 protein (p.Cys291Tyr). |
OMIM | RCV000012260 | SCV000032494 | pathogenic | Developmental and epileptic encephalopathy, 2 | 2008-09-23 | no assertion criteria provided | literature only | |
Rett |
RCV000012260 | SCV000188404 | uncertain significance | Developmental and epileptic encephalopathy, 2 | 2014-03-13 | no assertion criteria provided | curation | Conserved residue; In silico prediction: SIFT = deleterious, MutationTaster = disease-causing, PolyPhen2 = probably damaging, AlignGVGD = benign (C0) |