ClinVar Miner

Submissions for variant NM_000136.2(FANCC):c.535C>T (p.Arg179Ter) (rs769039987)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224844 SCV000281191 likely pathogenic not provided 2016-04-29 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000224844 SCV000861684 likely pathogenic not provided 2018-06-04 criteria provided, single submitter clinical testing
GeneDx RCV000224844 SCV000568699 likely pathogenic not provided 2016-09-02 criteria provided, single submitter clinical testing This variant is denoted FANCC c.535C>T at the cDNA level and p.Arg179Ter (R179X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant was identified in a mother and daughter with ovarian and breast cancer respectively, but was absent in a second daughter who also had breast cancer (Thompson 2012). Based on currently available information, we consider this variant to be likely pathogenic.
Invitae RCV000704130 SCV000833067 pathogenic Fanconi anemia 2018-01-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg179*) in the FANCC gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs769039987, ExAC 0.003%). This variant has been reported in a family affected with familial breast cancer and ovarian cancer, however, there is insufficient evidence to conclude whether this variant segregates with disease or not (PMID: 23028338). It has also been observed in an individual who underwent reproductive carrier-testing (PMID: 26990548). ClinVar contains an entry for this variant (Variation ID: 235535). 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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