ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.2464C>T (p.Arg822Cys)

gnomAD frequency: 0.00002  dbSNP: rs780609419
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001049501 SCV001213551 uncertain significance Developmental and epileptic encephalopathy, 2; Angelman syndrome-like 2021-11-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 822 of the CDKL5 protein (p.Arg822Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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 not expected to disrupt CDKL5 protein function. ClinVar contains an entry for this variant (Variation ID: 846246). This variant has not been reported in the literature in individuals affected with CDKL5-related conditions.
Ambry Genetics RCV002445261 SCV002732327 uncertain significance Inborn genetic diseases 2017-06-19 criteria provided, single submitter clinical testing The p.R822C variant (also known as c.2464C>T), located in coding exon 16 of the CDKL5 gene, results from a C to T substitution at nucleotide position 2464. The arginine at codon 822 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved through mammals but not in all 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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