Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001593904 | SCV001825098 | uncertain significance | not provided | 2024-01-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: Gordon2000[Book]) |
| Ambry Genetics | RCV002324158 | SCV002628221 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-23 | criteria provided, single submitter | clinical testing | The p.Q136P variant (also known as c.407A>C), located in coding exon 4 of the FANCC gene, results from an A to C substitution at nucleotide position 407. The glutamine at codon 136 is replaced by proline, an amino acid with similar 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. |
| Labcorp Genetics |
RCV002573357 | SCV003480381 | uncertain significance | Fanconi anemia | 2022-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 136 of the FANCC protein (p.Gln136Pro). This variant is present in population databases (no rsID available, 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: 1218708). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FANCC 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. |