Submissions for variant NM_001113378.2(FANCI):c.2326A>G (p.Met776Val)

gnomAD frequency: 0.00043  dbSNP: rs150544323

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000522385	SCV000620835	uncertain significance	not provided	2022-04-18	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000699113	SCV000827809	uncertain significance	Fanconi anemia	2022-09-23	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 776 of the FANCI protein (p.Met776Val). This variant is present in population databases (rs150544323, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with FANCI-related conditions. ClinVar contains an entry for this variant (Variation ID: 452060). 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 FANCI protein function. 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.
Genetic Services Laboratory, University of Chicago	RCV001821462	SCV002065624	uncertain significance	not specified	2019-09-12	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002481726	SCV002784233	uncertain significance	Fanconi anemia complementation group I	2022-02-09	criteria provided, single submitter	clinical testing