ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1607T>C (p.Leu536Pro) (rs587779903)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115346 SCV000149255 uncertain significance not provided 2018-04-02 criteria provided, single submitter clinical testing This variant is denoted FANCC c.1607T>C at the cDNA level, p.Leu536Pro (L536P) at the protein level, and results in the change of a Leucine to a Proline (CTT>CCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. FANCC Leu536Pro was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the cdc2 binding domain (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 evidence, it is unclear whether FANCC Leu536Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000699773 SCV000828498 uncertain significance Fanconi anemia 2018-08-03 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 536 of the FANCC protein (p.Leu536Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. 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: 127536). 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: "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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