Submissions for variant NM_001754.5(RUNX1):c.1210del (p.His404fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003516182	SCV004343880	likely pathogenic	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2023-06-27	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts a region of the RUNX1 protein in which other variant(s) (p.Tyr414*) have been determined to be pathogenic (PMID: 14504086, 15749889, 22689681, 23753029). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the RUNX1 gene (p.His404Thrfs*190). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 77 amino acid(s) of the RUNX1 protein and extend the protein by 112 additional amino acid residues.