Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004597751 | SCV005091974 | benign | CDKL5 disorder | 2024-02-23 | reviewed by expert panel | curation | The allele frequency of the p.Pro574Leu variant in CDKL5 is 0.021% in European (Finnish) sub population in gnomAD v2, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Pro574Leu variant is observed in the hemizygous state in at least 2 unaffected individuals (internal database - GeneDx) (BS2). The p.Pro574Leu variant is found in at least 3 patients with an alternate molecular basis of disease (internal database - GeneDx, internal database - Invitae) (BP5_strong). In summary, the p.Pro574Leu variant in CDKL5 is classified as benign based on the ACMG/AMP criteria (BS1, BS2, BP5_strong). |
Gene |
RCV001704064 | SCV000191067 | likely benign | not provided | 2020-12-28 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000866522 | SCV001007631 | benign | Developmental and epileptic encephalopathy, 2; Angelman syndrome-like | 2025-01-08 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002399513 | SCV002713639 | uncertain significance | Inborn genetic diseases | 2017-06-29 | criteria provided, single submitter | clinical testing | The p.P574L variant (also known as c.1721C>T), located in coding exon 11 of the CDKL5 gene, results from a C to T substitution at nucleotide position 1721. The proline at codon 574 is replaced by leucine, an amino acid with similar properties. This amino acid position is 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. |