Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001009996 | SCV001170135 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-03 | criteria provided, single submitter | clinical testing | The p.H384R variant (also known as c.1151A>G), located in coding exon 11 of the FANCC gene, results from an A to G substitution at nucleotide position 1151. The histidine at codon 384 is replaced by arginine, 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. |
Gene |
RCV001732012 | SCV001983170 | uncertain significance | not provided | 2021-10-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); 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 |
Labcorp Genetics |
RCV001860622 | SCV002136825 | uncertain significance | Fanconi anemia | 2022-11-04 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 384 of the FANCC protein (p.His384Arg). This variant is present in population databases (rs577302082, gnomAD 0.007%). 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: 818425). 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. |
Fulgent Genetics, |
RCV001273992 | SCV002775992 | uncertain significance | Fanconi anemia complementation group C | 2022-05-26 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001273992 | SCV001457653 | uncertain significance | Fanconi anemia complementation group C | 2020-09-16 | no assertion criteria provided | clinical testing |