Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV003156245 | SCV000570639 | uncertain significance | not provided | 2024-08-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports 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]) |
| Ambry Genetics | RCV001010546 | SCV001170766 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-22 | criteria provided, single submitter | clinical testing | The c.1252_1253delCCinsGA variant (also known as p.P418D), located in coding exon 12 of the FANCC gene, results from an in-frame deletion of CC and insertion of GA at nucleotide positions 1252 to 1253. This results in the substitution of the proline residue for an aspartic acid residue at codon 418, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688).. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001349481 | SCV001543829 | uncertain significance | Fanconi anemia | 2022-02-09 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 418 of the FANCC protein (p.Pro418Asp). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. 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: 421433). 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: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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. |