ClinVar Miner

Submissions for variant NM_018062.4(FANCL):c.860T>G (p.Val287Gly)

gnomAD frequency: 0.00001  dbSNP: rs61757387
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001228760 SCV001401177 uncertain significance Fanconi anemia 2022-10-29 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 287 of the FANCL protein (p.Val287Gly). This variant is present in population databases (rs61757387, gnomAD 0.003%). 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: 956027). 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.
Fulgent Genetics, Fulgent Genetics RCV002484247 SCV002782218 uncertain significance Fanconi anemia complementation group L 2022-01-05 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003918789 SCV004735155 uncertain significance FANCL-related disorder 2023-11-16 no assertion criteria provided clinical testing The FANCL c.875T>G variant is predicted to result in the amino acid substitution p.Val292Gly. This variant (also known as V287G) has been reported to result in increased protein aggregation (Table 1, Frost and Toth. 2020. PubMed ID: 32420600), but has not been reported in the literature in individuals with a FANCL-related phenotype. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-58390044-A-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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