Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV004735543 | SCV005367784 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2024-09-30 | reviewed by expert panel | curation | NM_001754.4:c.1007T>C is a missense variant which has an MAF of 0.0002133 (0.02%, 7/32818 alleles) in the Latino subpopulation of the gnomAD v2.1.1 cohort, which is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). This missense variant has a REVEL score >0.75 (0.791) (PP3). The variant has not been reported in the germ line of patients with familial platelet disorder with predisposition to hematologic malignancies in the literature, to the best of our knowledge. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1, PP3. |
| Labcorp Genetics |
RCV000462939 | SCV000550158 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2024-11-18 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 336 of the RUNX1 protein (p.Phe336Ser). This variant is present in population databases (rs752745196, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 409815). Invitae Evidence 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 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 RUNX1 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. |
| Prevention |
RCV003418193 | SCV004113716 | uncertain significance | RUNX1-related disorder | 2023-01-26 | criteria provided, single submitter | clinical testing | The RUNX1 c.1007T>C variant is predicted to result in the amino acid substitution p.Phe336Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.021% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-36164868-A-G) and is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/409815/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Gene |
RCV004591324 | SCV005078217 | uncertain significance | not provided | 2023-09-28 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |