ClinVar Miner

Submissions for variant NM_021922.2(FANCE):c.1331T>C (p.Leu444Pro) (rs745685973)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000649001 SCV000770822 uncertain significance Fanconi anemia, complementation group E 2017-10-25 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 444 of the FANCE protein (p.Leu444Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs745685973, ExAC 0.001%). This variant has not been reported in the literature in individuals with FANCE-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000609034 SCV000731356 uncertain significance not specified 2016-12-23 criteria provided, single submitter clinical testing The p.Leu444Pro (NM_021922.2 c.1331T>C) variant in FANCE has not been reported i n the literature. This variant has been identified in 0.001% (1/66670) of Europe an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs745685973). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role for Fanconi anemia. Computational prediction tools and conservation analysis suggest that the p.Leu444Pro variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical sign ificance of the p.Leu444Pro variant is uncertain.

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