ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1363G>T (p.Ala455Ser) (rs730881724)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000220014 SCV000279525 uncertain significance not provided 2018-01-30 criteria provided, single submitter clinical testing This variant is denoted FANCC c.1363G>T at the cDNA level, p.Ala455Ser (A455S) at the protein level, and results in the change of an Alanine to a Serine (GCA>TCA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. FANCC Ala455Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). FANCC Ala455Ser is not located in a known functional domain. 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 Ala455Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000456548 SCV000549954 uncertain significance Fanconi anemia 2018-09-20 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 455 of the FANCC protein (p.Ala455Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs730881724, ExAC 0.01%). This variant has not been reported in the literature in individuals with FANCC-related disease. ClinVar contains an entry for this variant (Variation ID: 234582). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Mendelics RCV000709081 SCV000838343 uncertain significance Fanconi anemia, complementation group C 2018-07-02 criteria provided, single submitter clinical testing

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