ClinVar Miner

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

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000202668 SCV000257631 pathogenic not provided 2015-07-15 criteria provided, single submitter clinical testing
Invitae RCV000526773 SCV000626233 pathogenic Fanconi anemia 2020-08-23 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.
GeneDx RCV000202668 SCV000779409 likely pathogenic not provided 2021-05-17 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); Observed in individuals with pancreatic and other cancers (Lu 2015, Hu 2018); This variant is associated with the following publications: (PMID: 26689913, 23634996, 29922827)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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.
Ambry Genetics RCV001010060 SCV001170204 pathogenic Hereditary cancer-predisposing syndrome 2019-02-14 criteria provided, single submitter clinical testing The p.G388* pathogenic mutation (also known as c.1162G>T), located in coding exon 12 of the FANCC gene, results from a G to T substitution at nucleotide position 1162. This changes the amino acid from a glycine to a stop codon within coding exon 12. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Counsyl RCV000409441 SCV000485348 likely pathogenic Fanconi anemia, complementation group C 2015-11-25 no assertion criteria provided clinical testing

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