Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetic Services Laboratory, |
RCV000504055 | SCV000594316 | pathogenic | Lissencephaly type 1 due to doublecortin gene mutation | 2015-10-19 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001575982 | SCV001803083 | pathogenic | not provided | 2021-02-05 | criteria provided, single submitter | clinical testing | Reported in the heterozygous state in a patient with double cortex syndrome (Gleeson et al., 1998); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 9489700) |
| Labcorp Genetics |
RCV001575982 | SCV002220142 | pathogenic | not provided | 2021-02-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with clinical features of lissencephaly and subcortical band heterotopia (PMID: 9489700). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr229Hisfs*12) in the DCX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DCX are known to be pathogenic (PMID: 11175293, 23365099). |
| Lifecell International Pvt. |
RCV000504055 | SCV003924039 | pathogenic | Lissencephaly type 1 due to doublecortin gene mutation | criteria provided, single submitter | clinical testing | A Hemizygote frameshift variant c.927_928delCT in Exon 3 of the DCX gene that results in the amino acid substitution p.Tyr310fs*12 was identified. The observed variant has a minor allele frequency of 0.00% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic (Variation ID: 434900). Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines. | |
| OMIM | RCV000012369 | SCV000032603 | pathogenic | Subcortical laminar heterotopia, X-linked | 1998-01-09 | no assertion criteria provided | literature only |