ClinVar Miner

Submissions for variant NM_018062.4(FANCL):c.661C>T (p.Arg221Trp)

gnomAD frequency: 0.00006  dbSNP: rs772025061
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001039772 SCV001203318 uncertain significance Fanconi anemia 2022-09-16 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 FANCL protein (p.Arg221Trp). This variant is present in population databases (rs772025061, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with FANCL-related conditions. ClinVar contains an entry for this variant (Variation ID: 838259). 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 FANCL protein function. Experimental studies have shown that this missense change affects FANCL function (PMID: 32420600). 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.
Sema4, Sema4 RCV001039772 SCV002527293 uncertain significance Fanconi anemia 2021-10-15 criteria provided, single submitter curation

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