ClinVar Miner

Submissions for variant NM_001195553.2(DCX):c.574C>T (p.Arg192Trp)

dbSNP: rs104894780
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000145864 SCV000193001 pathogenic Ectopic tissue 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000423650 SCV000520866 pathogenic not provided 2023-09-13 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect and show that this variant impairs the interaction of the DCX gene with microtubules and leads to defects in cortical neuronal migration (Taylor et al., 2000); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11175293, 10749977, 11001923, 19416314, 18685874, 12692530, 25868952, 12820024, 15607950, 9489700, 15045646, 9489699, 10946000, 23365099)
Labcorp Genetics (formerly Invitae), Labcorp RCV000423650 SCV005841070 pathogenic not provided 2024-11-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 192 of the DCX protein (p.Arg192Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of DCX-related conditions (PMID: 9489699, 9489700, 9618162, 11175293, 17111359, 18685874; internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 11598). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt DCX protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000012357 SCV000032591 pathogenic Lissencephaly type 1 due to doublecortin gene mutation 1998-01-09 no assertion criteria provided literature only
OMIM RCV000012358 SCV000032592 pathogenic Subcortical laminar heterotopia, X-linked 1998-01-09 no assertion criteria provided literature only

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