ClinVar Miner

Submissions for variant NM_021922.3(FANCE):c.1331T>C (p.Leu444Pro)

gnomAD frequency: 0.00001  dbSNP: rs745685973
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000649001 SCV000770822 uncertain significance Fanconi anemia complementation group E 2022-05-30 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 444 of the FANCE protein (p.Leu444Pro). This variant is present in population databases (rs745685973, gnomAD 0.002%). This missense change has been observed in individual(s) with multiple congenital anomalies and hydrocephalus (PMID: 30609409). ClinVar contains an entry for this variant (Variation ID: 517206). 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: "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.

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