Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV004693380 | SCV005196429 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2024-08-01 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.122C>T (p.Thr41Met) is a missense variant which does not meet any ACMG/AMP criteria. 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: None. |
| Labcorp Genetics |
RCV000818880 | SCV000959517 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2024-07-03 | 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 41 of the RUNX1 protein (p.Thr41Met). 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. 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: 661459). 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 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. |