ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.1322T>C (p.Leu441Pro)

dbSNP: rs777551786
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV004693465 SCV005196433 uncertain significance Hereditary thrombocytopenia and hematologic cancer predisposition syndrome 2024-08-12 reviewed by expert panel curation NM_001754.5(RUNX1):c.1322T>C (p.Leu441Pro) 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 (formerly Invitae), Labcorp RCV001038470 SCV001201940 uncertain significance Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2024-04-15 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 441 of the RUNX1 protein (p.Leu441Pro). This variant is present in population databases (rs777551786, 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: 837191). 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) performed at Invitae indicates that this missense variant is not expected to disrupt RUNX1 protein function with a negative predictive value of 80%. 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.
PreventionGenetics, part of Exact Sciences RCV003413823 SCV004107404 uncertain significance RUNX1-related disorder 2023-09-13 criteria provided, single submitter clinical testing The RUNX1 c.1322T>C variant is predicted to result in the amino acid substitution p.Leu441Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.018% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-36164553-A-G) and is interpreted as uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/837191/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics RCV004963005 SCV005495380 uncertain significance Inborn genetic diseases 2024-08-19 criteria provided, single submitter clinical testing The c.1322T>C (p.L441P) alteration is located in exon 9 (coding exon 8) of the RUNX1 gene. This alteration results from a T to C substitution at nucleotide position 1322, causing the leucine (L) at amino acid position 441 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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