ClinVar Miner

Submissions for variant NM_004859.4(CLTC):c.2669C>T (p.Pro890Leu)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Undiagnosed Diseases Network, NIH RCV000578214 SCV001432146 pathogenic Intellectual disability, autosomal dominant 56 2020-02-24 criteria provided, single submitter clinical testing
Laboratoire de Génétique Moléculaire, CHU Bordeaux RCV001281635 SCV001468971 pathogenic not provided criteria provided, single submitter clinical testing
GeneDx 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, Charité - Universitätsmedizin Berlin 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 (formerly Invitae), Labcorp 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, Murdoch Childrens Research Institute 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-Manton Center, Boston Children's Hospital RCV000578214 SCV000930678 uncertain significance Intellectual disability, autosomal dominant 56 2019-02-05 no assertion criteria provided clinical testing
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine RCV000578214 SCV001442973 likely pathogenic Intellectual disability, autosomal dominant 56 2020-09-14 no assertion criteria provided clinical testing
Service de Génétique Moléculaire, Hôpital Robert Debré RCV000578214 SCV001450717 pathogenic Intellectual disability, autosomal dominant 56 2020-07-03 no assertion criteria provided clinical testing

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