Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| SIB Swiss Institute of Bioinformatics | RCV000755736 | SCV000883246 | uncertain significance | Intellectual disability, autosomal dominant 57 | 2018-10-15 | criteria provided, single submitter | curation | This variant is interpreted as Uncertain Significance - Insufficient Evidence, for Mental retardation, autosomal dominant 57. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM6 => Assumed de novo, but without confirmation of paternity and maternity (https://www.ncbi.nlm.nih.gov/pubmed/29861108). |
| Gene |
RCV001785717 | SCV002027746 | pathogenic | not provided | 2021-11-15 | criteria provided, single submitter | clinical testing | A different missense change at this residue (R339Q) has been reported in the published literature (Reijnders et al., 2018); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29861108, 31406558) |
| Laboratoire de Génétique Moléculaire, |
RCV000755736 | SCV003836664 | likely pathogenic | Intellectual disability, autosomal dominant 57 | 2022-02-15 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001785717 | SCV003917958 | likely pathogenic | not provided | 2023-03-01 | criteria provided, single submitter | clinical testing | TLK2: PM2, PM5, PS4:Moderate, PP2 |
| Victorian Clinical Genetics Services, |
RCV000755736 | SCV005086029 | pathogenic | Intellectual disability, autosomal dominant 57 | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with intellectual developmental disorder 57 (MIM#618050). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to tryptophan. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. p.(Arg339Gln) has been reported de novo in an individual with a neurodevelopmental disorder (PMID: 29861108). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported as de novo in three individuals with neurodevelopmental disorders (PMID: 29861108, 31406558). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |