ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1162G>T (p.Gly388Ter) (rs371897078)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409441 SCV000485348 likely pathogenic Fanconi anemia, complementation group C 2015-11-25 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000202668 SCV000257631 pathogenic not provided 2015-07-15 criteria provided, single submitter clinical testing
GeneDx RCV000202668 SCV000779409 likely pathogenic not provided 2017-08-17 criteria provided, single submitter clinical testing This variant is denoted FANCC c.1162G>T at the cDNA level and p.Gly388Ter (G388X) at the protein level. The substitution creates a nonsense variant, which changes a Glycine to a premature stop codon (GGA>TGA) , and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered likely pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000409441 SCV000919323 likely pathogenic Fanconi anemia, complementation group C 2018-10-04 criteria provided, single submitter clinical testing Variant summary: FANCC c.1162G>T (p.Gly388X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., p.Arg548X). The variant allele was found at a frequency of 1.1e-05 in 277132 control chromosomes. c.1162G>T has been reported in the literature in individuals affected with and pancreatic cancer and AML (Hu_2018, Lu_2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000526773 SCV000626233 pathogenic Fanconi anemia 2017-09-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly388*) in the FANCC gene. It is expected to result in an absent or disrupted protein product. 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: 218427). 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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