ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.397C>T (p.Leu133Phe)

gnomAD frequency: 0.00001  dbSNP: rs587779906
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115353 SCV000149262 uncertain significance not provided 2023-11-08 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV000464178 SCV000549949 uncertain significance Fanconi anemia 2023-10-04 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 133 of the FANCC protein (p.Leu133Phe). This variant is not present in population databases (gnomAD no frequency). 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: 127542). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FANCC 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.
Ambry Genetics RCV002354291 SCV002620793 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-11 criteria provided, single submitter clinical testing The p.L133F variant (also known as c.397C>T), located in coding exon 4 of the FANCC gene, results from a C to T substitution at nucleotide position 397. The leucine at codon 133 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is not 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.
Natera, Inc. RCV001276461 SCV001462832 uncertain significance Fanconi anemia complementation group C 2020-09-16 no assertion criteria provided clinical testing

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