ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.571A>C (p.Ile191Leu)

gnomAD frequency: 0.00001  dbSNP: rs752429169
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001244148 SCV001417350 uncertain significance Fanconi anemia 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with leucine at codon 191 of the FANCC protein (p.Ile191Leu). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is present in population databases (rs752429169, ExAC 0.002%). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV001760276 SCV001991113 uncertain significance not provided 2019-05-29 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002348829 SCV002650624 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-01 criteria provided, single submitter clinical testing The p.I191L variant (also known as c.571A>C), located in coding exon 6 of the FANCC gene, results from an A to C substitution at nucleotide position 571. The isoleucine at codon 191 is replaced by leucine, an amino acid with highly 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.
Natera, Inc. RCV001244148 SCV002081245 uncertain significance Fanconi anemia 2021-09-17 no assertion criteria provided clinical testing

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