ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1217T>C (p.Met406Thr)

dbSNP: rs1159499581
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001360267 SCV001556178 uncertain significance Fanconi anemia 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 406 of the FANCC protein (p.Met406Thr). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Ambry Genetics RCV002357221 SCV002655015 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-15 criteria provided, single submitter clinical testing The p.M406T variant (also known as c.1217T>C), located in coding exon 12 of the FANCC gene, results from a T to C substitution at nucleotide position 1217. The methionine at codon 406 is replaced by threonine, 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.

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