ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1643G>A (p.Arg548Gln) (rs730881729)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160494 SCV000211059 uncertain significance not provided 2018-08-07 criteria provided, single submitter clinical testing This variant is denoted FANCC c.1643G>A at the cDNA level, p.Arg548Gln (R548Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. FANCC Arg548Gln was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in a region that interacts with cdc2 (Gordon 2000). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether FANCC Arg548Gln is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000630940 SCV000751915 uncertain significance Fanconi anemia 2018-01-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 548 of the FANCC protein (p.Arg548Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FANCC-related disease. ClinVar contains an entry for this variant (Variation ID: 182492). 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: "Tolerated"; PolyPhen-2: "Possibly 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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