Submissions for variant NM_000135.4(FANCA):c.55C>T (p.Arg19Trp)

gnomAD frequency: 0.00001  dbSNP: rs1300733063

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001299597	SCV001488696	uncertain significance	Fanconi anemia	2021-09-25	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with tryptophan at codon 19 of the FANCA protein (p.Arg19Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with FANCA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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	RCV003238338	SCV002010164	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001760347	SCV002784831	uncertain significance	Fanconi anemia complementation group A	2022-03-25	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001299597	SCV002093155	uncertain significance	Fanconi anemia	2020-03-20	no assertion criteria provided	clinical testing