Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV000210876 | SCV001522066 | pathogenic | Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 | 2019-12-19 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
Kariminejad - |
RCV001814075 | SCV001755214 | pathogenic | Abnormality of the nervous system | 2021-07-10 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000210876 | SCV002018935 | pathogenic | Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 | 2021-02-07 | criteria provided, single submitter | clinical testing | |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000210876 | SCV002072920 | pathogenic | Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 | criteria provided, single submitter | clinical testing | The splice donor variant c.1897+1G>A in TBCK (NM_001163435.3) has been previously reported in affected patients (Bhoj E et al). The variant has been submitted to ClinVar as Pathogenic/Likely pathogenic. The c.1897+1G>A variant is observed in 2/29,354 (0.0068%) alleles from individuals of Latino background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant affects an invariant splice nucleotide and is predicted to cause loss of function. Loss of function mutations have been reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. | |
3billion | RCV000210876 | SCV002521425 | pathogenic | Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000183338). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Invitae | RCV002516437 | SCV003525523 | pathogenic | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 21 of the TBCK gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TBCK are known to be pathogenic (PMID: 27040692, 30103036). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individual(s) with TBCK-related conditions (PMID: 25558065). This variant is also known as c.1708+1G>A. ClinVar contains an entry for this variant (Variation ID: 183338). Studies have shown that disruption of this splice site alters TBCK gene expression (PMID: 27040691). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Center for Genomic Medicine, |
RCV000210876 | SCV004804719 | pathogenic | Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 | 2024-03-17 | criteria provided, single submitter | research | |
Department Of Translational Genomics |
RCV000162173 | SCV000196459 | likely pathogenic | Global developmental delay; Seizure; Ventral septal defect; Delayed reflexes; Dysmorphism; Hypotonia | 2014-12-01 | no assertion criteria provided | research | |
OMIM | RCV000210876 | SCV000267181 | pathogenic | Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 | 2015-01-13 | no assertion criteria provided | literature only |