Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000566315 | SCV000673342 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-12 | criteria provided, single submitter | clinical testing | The p.W364R variant (also known as c.1090T>C), located in coding exon 11 of the FANCC gene, results from a T to C substitution at nucleotide position 1090. The tryptophan at codon 364 is replaced by arginine, an amino acid with dissimilar 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. |
Invitae | RCV000797804 | SCV000937385 | uncertain significance | Fanconi anemia | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan with arginine at codon 364 of the FANCC protein (p.Trp364Arg). The tryptophan residue is moderately conserved and there is a moderate physicochemical difference between tryptophan and arginine. 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. ClinVar contains an entry for this variant (Variation ID: 485549). 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 arginine 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. |
Gene |
RCV001770521 | SCV002002693 | uncertain significance | not provided | 2021-03-16 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with ovarian cancer (Song 2020); This variant is associated with the following publications: (PMID: 32546565) |
Natera, |
RCV000797804 | SCV002081179 | uncertain significance | Fanconi anemia | 2018-09-22 | no assertion criteria provided | clinical testing |