Submissions for variant NM_021922.3(FANCE):c.661C>T (p.Arg221Trp)

gnomAD frequency: 0.00002  dbSNP: rs771767241

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001302300	SCV001491500	uncertain significance	Fanconi anemia complementation group E	2024-10-23	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 221 of the FANCE protein (p.Arg221Trp). This variant is present in population databases (rs771767241, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FANCE-related conditions. ClinVar contains an entry for this variant (Variation ID: 1005434). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt FANCE 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003238340	SCV002011417	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002255642	SCV002527969	uncertain significance	Fanconi anemia	2021-07-23	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV001302300	SCV002782864	uncertain significance	Fanconi anemia complementation group E	2024-03-22	criteria provided, single submitter	clinical testing