Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000199045 | SCV000254250 | uncertain significance | Fanconi anemia | 2024-02-09 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 342 of the FANCC protein (p.Pro342Ala). This variant is present in population databases (no rsID available, gnomAD 0.02%). 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: 216280). 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 expected to disrupt FANCC protein function with a positive predictive value of 80%. 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 | RCV002381685 | SCV002690181 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-04 | criteria provided, single submitter | clinical testing | The p.P342A variant (also known as c.1024C>G), located in coding exon 10 of the FANCC gene, results from a C to G substitution at nucleotide position 1024. The proline at codon 342 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Gene |
RCV003322759 | SCV004028018 | uncertain significance | not provided | 2023-02-21 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: Gordon2000[Book]) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005237704 | SCV005886431 | uncertain significance | not specified | 2025-02-17 | criteria provided, single submitter | clinical testing | Variant summary: FANCC c.1024C>G (p.Pro342Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251212 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1024C>G in individuals affected with Fanconi Anemia Group C and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 216280). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Natera, |
RCV000199045 | SCV002081188 | uncertain significance | Fanconi anemia | 2017-11-21 | no assertion criteria provided | clinical testing |