Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001221552 | SCV001393605 | uncertain significance | Fanconi anemia | 2021-10-02 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 547 of the FANCC protein (p.Ala547Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). 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: "Probably Damaging"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV002402678 | SCV002707694 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-06 | criteria provided, single submitter | clinical testing | The p.A547V variant (also known as c.1640C>T), located in coding exon 14 of the FANCC gene, results from a C to T substitution at nucleotide position 1640. The alanine at codon 547 is replaced by valine, an amino acid with similar properties. This amino acid position is 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. |
| Gene |
RCV005005091 | SCV005628942 | uncertain significance | not provided | 2024-07-16 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter 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]) |