Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ai |
RCV001265617 | SCV001251170 | pathogenic | Congenital heart defects and skeletal malformations syndrome | 2020-05-20 | criteria provided, single submitter | research | This variant was seen de novo in a 3-year-old female with failure to thrive, severe feeding difficulties, axial hypotonia, mild clinodactyly, tapered fingers, gastroesophageal reflux disease, umbilical hernia, and dysmorphic facial features. |
| Gene |
RCV002284471 | SCV002574403 | pathogenic | not provided | 2022-09-19 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that this variant leads to a gain of function with increased kinase activity (Chen et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); 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: 28714951, 28191890, 32643838, 25363768, 31785789) |
| Labcorp Genetics |
RCV002284471 | SCV003459991 | uncertain significance | not provided | 2023-02-14 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 136 of the ABL1 protein (p.Thr136Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ABL1-related conditions (PMID: 32643838). ClinVar contains an entry for this variant (Variation ID: 929418). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ABL1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| OMIM | RCV001265617 | SCV002014672 | pathogenic | Congenital heart defects and skeletal malformations syndrome | 2021-11-11 | no assertion criteria provided | literature only |