Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000824523 | SCV000965423 | uncertain significance | Fanconi anemia | 2022-02-19 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 319 of the FANCC protein (p.Thr319Met). This variant is present in population databases (rs745910444, gnomAD 0.007%). 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: 666102). 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 methionine 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 |
RCV001759625 | SCV001985253 | uncertain significance | not provided | 2023-09-20 | 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; This variant is associated with the following publications: (PMID: Gordon2000[Book], 27397505) |
Ambry Genetics | RCV002372363 | SCV002690781 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-03 | criteria provided, single submitter | clinical testing | The p.T319M variant (also known as c.956C>T), located in coding exon 9 of the FANCC gene, results from a C to T substitution at nucleotide position 956. The threonine at codon 319 is replaced by methionine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, methionine is the reference amino acid in other 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, |
RCV001274467 | SCV001458690 | uncertain significance | Fanconi anemia complementation group C | 2020-09-16 | no assertion criteria provided | clinical testing |