Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000160480 | SCV000211045 | uncertain significance | not provided | 2018-05-17 | criteria provided, single submitter | clinical testing | This variant is denoted FANCC c.802T>A at the cDNA level, p.Cys268Ser (C268S) at the protein level, and results in the change of a Cysteine to a Serine (TGT>AGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. FANCC Cys268Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the region of interaction with Hsp70 and GRP94 (Gordon 2000). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether FANCC Cys268Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Invitae | RCV000459016 | SCV000549960 | uncertain significance | Fanconi anemia | 2022-01-13 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 268 of the FANCC protein (p.Cys268Ser). This variant is present in population databases (rs730881718, gnomAD 0.002%). 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: 182479). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
Ambry Genetics | RCV001027088 | SCV001189590 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-21 | criteria provided, single submitter | clinical testing | The p.C268S variant (also known as c.802T>A), located in coding exon 7 of the FANCC gene, results from a T to A substitution at nucleotide position 802. The cysteine at codon 268 is replaced by serine, 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001274477 | SCV001458700 | uncertain significance | Fanconi anemia complementation group C | 2020-09-16 | no assertion criteria provided | clinical testing |