ClinVar Miner

Submissions for variant NM_003718.5(CDK13):c.2603G>A (p.Arg868Gln)

dbSNP: rs1786184821
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001785390 SCV002026420 uncertain significance Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder 2021-10-19 criteria provided, single submitter clinical testing _x000D_This variant was also indentified in thesimilary affected brother Criteria applied: PM1, PM2_SUP, PP2, PP3
Molecular Genetics, Royal Melbourne Hospital RCV001785390 SCV004812415 likely pathogenic Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder 2023-03-30 criteria provided, single submitter clinical testing This sequence change in CDK13 is predicted to replace arginine with glutamine at codon 868, p.(Arg868Gln). The arginine residue is highly conserved (100 vertebrates, UCSC), and is located in the protein kinase domain, a region (amino acids 705-998), that is defined as a mutational hotspot and critical functional domain (PMID: 29021403). There is a small physicochemical difference between arginine and glutamine. This variant is absent from gnomAD v2.1 and v3.1. This variant has been reported in at least two probands with a consistent intellectual developmental disorder phenotype (ClinVar: SCV002026420.1; Royal Melbourne Hospital). At least one patient with this variant displayed dysmorphic facial features and other features highly characteristic of CDK13-related disorder (PMID:30702837; Royal Melbourne Hospital). Multiple lines of computational evidence have conflicting predictions for the missense substitution (3/5 algorithms predict deleterious). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: PM1, PP4_Moderate, PS4_Supporting, PM2_Supporting.
GeneDx RCV004728818 SCV005331794 pathogenic not provided 2024-02-25 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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