ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.1721C>T (p.Pro574Leu)

gnomAD frequency: 0.00005  dbSNP: rs199897804
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Total submissions: 4
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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 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).
GeneDx RCV001704064 SCV000191067 likely benign not provided 2020-12-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp 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.

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