Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Undiagnosed Diseases Network, |
RCV000578214 | SCV001432146 | pathogenic | Intellectual disability, autosomal dominant 56 | 2020-02-24 | criteria provided, single submitter | clinical testing | |
Laboratoire de Génétique Moléculaire, |
RCV001281635 | SCV001468971 | pathogenic | not provided | criteria provided, single submitter | clinical testing | ||
Gene |
RCV001281635 | SCV002526557 | pathogenic | not provided | 2022-06-14 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as P890L; This variant is associated with the following publications: (PMID: 28191890, 31036916, 31231135, 30979967, 26822784, 28135719, 30337205, 31776469, 31785789, 33004838, 29100083) |
Institute for Medical Genetics and Human Genetics, |
RCV000578214 | SCV002574942 | pathogenic | Intellectual disability, autosomal dominant 56 | 2022-09-16 | criteria provided, single submitter | clinical testing | |
MGZ Medical Genetics Center | RCV000578214 | SCV002580042 | likely pathogenic | Intellectual disability, autosomal dominant 56 | 2022-06-10 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001281635 | SCV003297510 | pathogenic | not provided | 2022-09-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 488418). This variant is also known as c.2669C>T (p.Pro890Leu). This missense change has been observed in individual(s) with CLTC-related conditions (PMID: 29100083). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 894 of the CLTC protein (p.Pro894Leu). |
Victorian Clinical Genetics Services, |
RCV000578214 | SCV005086158 | pathogenic | Intellectual disability, autosomal dominant 56 | 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 56 (MIM# 617854). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity (PMID:31776469). (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to leucine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0801 - This variant has strong previous evidence of pathogenicity and has been reported as de novo in multiple unrelated individuals with intellectual disability and related symptoms (PMID:29100083, PMID:30337205, PMID:31036916 and PMID:31776469). (SP) 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 |
OMIM | RCV000578214 | SCV000680085 | pathogenic | Intellectual disability, autosomal dominant 56 | 2021-10-20 | no assertion criteria provided | literature only | |
Gene Discovery Core- |
RCV000578214 | SCV000930678 | uncertain significance | Intellectual disability, autosomal dominant 56 | 2019-02-05 | no assertion criteria provided | clinical testing | |
Department of Genetics, |
RCV000578214 | SCV001442973 | likely pathogenic | Intellectual disability, autosomal dominant 56 | 2020-09-14 | no assertion criteria provided | clinical testing | |
Service de Génétique Moléculaire, |
RCV000578214 | SCV001450717 | pathogenic | Intellectual disability, autosomal dominant 56 | 2020-07-03 | no assertion criteria provided | clinical testing |