Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000204465 | SCV000261200 | uncertain significance | Fanconi anemia | 2016-12-07 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FANCC-related disease. This sequence change replaces proline with alanine at codon 142 of the FANCC protein (p.Pro142Ala). The proline residue is moderately conserved and there is a small physicochemical difference between proline and alanine. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. |
Ambry Genetics | RCV002327064 | SCV002632884 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-12 | criteria provided, single submitter | clinical testing | The p.P142A variant (also known as c.424C>G), located in coding exon 4 of the FANCC gene, results from a C to G substitution at nucleotide position 424. The proline at codon 142 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is conserved. 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, |
RCV000204465 | SCV002081272 | uncertain significance | Fanconi anemia | 2021-07-06 | no assertion criteria provided | clinical testing |