ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1368G>T (p.Met456Ile)

dbSNP: rs863224609
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000199855 SCV000254253 uncertain significance Fanconi anemia 2021-05-17 criteria provided, single submitter clinical testing 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. 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"). This variant has not been reported in the literature in individuals with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 216283). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 456 of the FANCC protein (p.Met456Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine.
Ambry Genetics RCV002381686 SCV002702229 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-16 criteria provided, single submitter clinical testing The p.M456I variant (also known as c.1368G>T), located in coding exon 13 of the FANCC gene, results from a G to T substitution at nucleotide position 1368. The methionine at codon 456 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
Fulgent Genetics, Fulgent Genetics RCV002492914 SCV002782624 uncertain significance Fanconi anemia complementation group C 2022-05-10 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV002492914 SCV003843134 uncertain significance Fanconi anemia complementation group C 2022-01-03 criteria provided, single submitter clinical testing The FANCC c.1368G>T (p.Met456Ile) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Natera, Inc. RCV000199855 SCV002081150 uncertain significance Fanconi anemia 2018-09-28 no assertion criteria provided clinical testing

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