Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000518928 | SCV000617153 | uncertain significance | not provided | 2023-03-31 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Not observed in any cases, but was observed in unaffected controls from a melanoma study (Pritchard et al., 2018); This variant is associated with the following publications: (PMID: 29641532, Gordon2000[Book]) |
Invitae | RCV000687151 | SCV000814703 | uncertain significance | Fanconi anemia | 2023-09-08 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 449254). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. This variant is present in population databases (rs771619614, gnomAD 0.006%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 91 of the FANCC protein (p.Ile91Val). |
Ambry Genetics | RCV001016395 | SCV001177348 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-14 | criteria provided, single submitter | clinical testing | The p.I91V variant (also known as c.271A>G), located in coding exon 3 of the FANCC gene, results from an A to G substitution at nucleotide position 271. The isoleucine at codon 91 is replaced by valine, an amino acid with highly similar properties. This alteration was identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS One, 2018 Apr;13:e0194098). 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, |
RCV000687151 | SCV002081288 | uncertain significance | Fanconi anemia | 2018-10-18 | no assertion criteria provided | clinical testing |