ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1351T>G (p.Trp451Gly)

dbSNP: rs2040072996
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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 RCV001300971 SCV001490126 uncertain significance Fanconi anemia 2021-08-12 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with glycine at codon 451 of the FANCA protein (p.Trp451Gly). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and glycine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of FANCA-related conditions (Invitae). 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 FANCA 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.
GeneDx RCV001751579 SCV001996340 uncertain significance not provided 2020-01-30 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge

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