Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001008883 | SCV001168689 | pathogenic | not provided | 2022-08-16 | criteria provided, single submitter | clinical testing | 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 (gnomAD); This variant is associated with the following publications: (PMID: 33753861) |
| Institute of Medical Genetics and Applied Genomics, |
RCV001008883 | SCV001446533 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001860598 | SCV002234012 | pathogenic | Spastic paraplegia | 2021-05-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu1131Alafs*72) in the KDM5C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KDM5C are known to be pathogenic (PMID: 15586325, 18697827). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with KDM5C-related conditions. ClinVar contains an entry for this variant (Variation ID: 817677). This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002549292 | SCV003646373 | pathogenic | Inborn genetic diseases | 2022-11-21 | criteria provided, single submitter | clinical testing | The c.3392_3393delAG (p.E1131Afs*72) alteration, located in exon 22 (coding exon 22) of the KDM5C gene, consists of a deletion of 2 nucleotides from position 3392 to 3393, causing a translational frameshift with a predicted alternate stop codon after 72 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration was reported in a male patient with features consistent with KDM5C-related neurodevelopmental disorder (Chen, 2021; Wu, 2022). Based on the available evidence, this alteration is classified as pathogenic. |
| Service de Génétique Moléculaire, |
RCV001256997 | SCV001433553 | likely pathogenic | Rare genetic intellectual disability | no assertion criteria provided | clinical testing |