ClinVar Miner

Submissions for variant NM_005263.5(GFI1):c.1250C>T (p.Thr417Met)

gnomAD frequency: 0.00008  dbSNP: rs777241871
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000986338 SCV001135313 likely benign Neutropenia, severe congenital, 2, autosomal dominant 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV000986338 SCV001393613 uncertain significance Neutropenia, severe congenital, 2, autosomal dominant 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 417 of the GFI1 protein (p.Thr417Met). This variant is present in population databases (rs777241871, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with GFI1-related conditions. ClinVar contains an entry for this variant (Variation ID: 801501). 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 GFI1 protein function with a positive 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.
Ambry Genetics RCV002549664 SCV003731310 uncertain significance Inborn genetic diseases 2021-08-28 criteria provided, single submitter clinical testing The c.1250C>T (p.T417M) alteration is located in exon 7 (coding exon 6) of the GFI1 gene. This alteration results from a C to T substitution at nucleotide position 1250, causing the threonine (T) at amino acid position 417 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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