ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1406C>T (p.Thr469Met)

gnomAD frequency: 0.00005  dbSNP: rs149917017
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487102 SCV000566574 uncertain significance not provided 2023-10-05 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with ovarian cancer (PMID: 32546565); This variant is associated with the following publications: (PMID: 32546565)
Mendelics RCV000988195 SCV001137832 uncertain significance Fanconi anemia complementation group A 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001011411 SCV001171729 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-27 criteria provided, single submitter clinical testing The p.T469M variant (also known as c.1406C>T), located in coding exon 13 of the FANCC gene, results from a C to T substitution at nucleotide position 1406. The threonine at codon 469 is replaced by methionine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001247526 SCV001420953 uncertain significance Fanconi anemia 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 469 of the FANCC protein (p.Thr469Met). This variant is present in population databases (rs149917017, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 419042). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001328458 SCV001519599 uncertain significance not specified 2021-03-08 criteria provided, single submitter clinical testing Variant summary: FANCC c.1406C>T (p.Thr469Met) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 251262 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in FANCC causing Fanconi Anemia Group C (5.2e-05 vs 0.0018), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1406C>T in individuals affected with Fanconi Anemia Group C and no experimental evidence demonstrating its impact on protein function have 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 uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV002481503 SCV002783165 uncertain significance Fanconi anemia complementation group C 2021-12-20 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV000487102 SCV002074997 not provided not provided no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 10-21-2016 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Natera, Inc. RCV001247526 SCV002081148 uncertain significance Fanconi anemia 2018-11-15 no assertion criteria provided clinical testing

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