Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004695186 | SCV005196446 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2024-08-12 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.140T>A (p.Leu47Gln) 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 |
RCV001213519 | SCV001385154 | uncertain significance | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | 2022-07-12 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 47 of the RUNX1 protein (p.Leu47Gln). This variant is present in population databases (rs770530237, gnomAD 0.0009%). 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: 943347). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. |
Ambry Genetics | RCV002561816 | SCV003745423 | uncertain significance | Inborn genetic diseases | 2022-10-27 | criteria provided, single submitter | clinical testing | The c.140T>A (p.L47Q) alteration is located in exon 4 (coding exon 3) of the RUNX1 gene. This alteration results from a T to A substitution at nucleotide position 140, causing the leucine (L) at amino acid position 47 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |