ClinVar Miner

Submissions for variant NM_002017.5(FLI1):c.1010G>A (p.Arg337Gln)

dbSNP: rs1064797086
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
NIHR Bioresource Rare Diseases, University of Cambridge RCV000851630 SCV000899398 likely pathogenic 11q partial monosomy syndrome 2019-02-01 criteria provided, single submitter research
Genetic Services Laboratory, University of Chicago RCV001821405 SCV002067428 likely pathogenic not provided 2020-01-14 criteria provided, single submitter clinical testing DNA sequence analysis of the FLI1 gene demonstrated a sequence change, c.1010G>A, in exon 9 that results in an amino acid change, p.Arg337Gln. This sequence change has not been described in population databases (gnomAD, ExAC). The p.Arg337Gln change has been reported in the heterozygous state in a family with macrothrombocytopenia. Functional analysis of this sequence change demonstrated a significant reduction in transcriptional activity (PMID: 28255014). The p.Arg337Gln change affects a highly conserved amino acid residue located in a domain of the FLI1 protein that is known to be functional. The p.Arg337Gln substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL).
Invitae RCV001821405 SCV004294998 uncertain significance not provided 2023-03-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 337 of the FLI1 protein (p.Arg337Gln). 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. 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 expected to disrupt FLI1 protein function. ClinVar contains an entry for this variant (Variation ID: 424635). This missense change has been observed in individual(s) with clinical features of FLI1-related conditions (PMID: 28255014, 31064749). This variant is not present in population databases (gnomAD no frequency).
OMIM RCV000487465 SCV000574550 pathogenic Bleeding disorder, platelet-type, 21 2017-04-25 no assertion criteria provided literature only

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