ClinVar Miner

Submissions for variant NM_001754.4(RUNX1):c.351+1G>C (rs1060502579)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV000473754 SCV000965628 likely pathogenic Familial platelet disorder with associated myeloid malignancy 2019-08-01 reviewed by expert panel curation The NM_001754.4(RUNX1):c.351+1G>C variant is a canonical splice site variant that is predicted to introduce a frameshift and a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2.
Invitae RCV000473754 SCV000550165 likely pathogenic Familial platelet disorder with associated myeloid malignancy 2016-10-12 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the RUNX1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with a RUNX1-related disease. Two different variants affecting this nucleotide (c.351+1G>T, c.351+1G>A) have been reported in individuals affected with thrombocytopenia (PMID: 24100448) and familial platelet disorder with propensity to myeloid malignancy (PMID: 18723428). In summary, donor and acceptor splice site variants are typically loss-of-function (PMID: 16199547), and loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic.
PreventionGenetics RCV000680407 SCV000807778 likely pathogenic not provided 2016-10-09 criteria provided, single submitter clinical testing

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