Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000467727 | SCV000549967 | uncertain significance | Fanconi anemia | 2021-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 170 of the FANCC protein (p.Asn170Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs749322338, ExAC 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: 409660). 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. 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. |
Gene |
RCV001560667 | SCV001783124 | uncertain significance | not provided | 2019-10-30 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this 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: 15695377) |
Genome- |
RCV001276457 | SCV001786855 | uncertain significance | Fanconi anemia complementation group C | 2021-07-14 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002339166 | SCV002642455 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-30 | criteria provided, single submitter | clinical testing | The p.N170S variant (also known as c.509A>G), located in coding exon 5 of the FANCC gene, results from an A to G substitution at nucleotide position 509. The asparagine at codon 170 is replaced by serine, an amino acid with highly 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001560667 | SCV004218682 | uncertain significance | not provided | 2023-06-21 | criteria provided, single submitter | clinical testing | This variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000004 (1/251178 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
Natera, |
RCV001276457 | SCV001462828 | uncertain significance | Fanconi anemia complementation group C | 2020-09-16 | no assertion criteria provided | clinical testing |