ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1257dup (p.Thr420fs) (rs765551897)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657293 SCV000779024 likely pathogenic not provided 2017-02-16 criteria provided, single submitter clinical testing This duplication of one nucleotide in FANCC is denoted c.1257dupC at the cDNA level and p.Thr420HisfsX15 (T420HfsX15) at the protein level. The normal sequence, with the base that is duplicated in brackets, is ACCCCC[dupC]ACGG. The duplication causes a frameshift which changes a Threonine to a Histidine at codon 420, and creates a premature stop codon at position 15 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this duplication to be a likely pathogenic variant.
Invitae RCV000824456 SCV000965355 pathogenic Fanconi anemia 2018-10-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr420Hisfs*15) in the FANCC gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs776037287, 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: 545768). Loss-of-function variants in FANCC are known to be pathogenic (PMID: 17924555). For these reasons, this variant has been classified as Pathogenic.

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