ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.80C>T (p.Thr27Ile)

dbSNP: rs1489419613
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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 RCV000702909 SCV000831785 uncertain significance Fanconi anemia 2021-09-02 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 27 of the FANCC protein (p.Thr27Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; 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.
Ambry Genetics RCV001027176 SCV001189690 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-29 criteria provided, single submitter clinical testing The p.T27I variant (also known as c.80C>T), located in coding exon 1 of the FANCC gene, results from a C to T substitution at nucleotide position 80. The threonine at codon 27 is replaced by isoleucine, an amino acid with similar properties. This alteration was identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS One, 2018 Apr;13:e0194098). This amino acid position is well 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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