Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000534368 | SCV000626228 | uncertain significance | Fanconi anemia | 2022-05-21 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 340 of the FANCC protein (p.Tyr340Cys). This variant is present in population databases (rs746828156, gnomAD 0.01%). 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: 456148). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 |
RCV002266982 | SCV002549293 | uncertain significance | not provided | 2022-07-12 | 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 |
Ambry Genetics | RCV002367772 | SCV002660116 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-08-26 | criteria provided, single submitter | clinical testing | The p.Y340C variant (also known as c.1019A>G), located in coding exon 10 of the FANCC gene, results from an A to G substitution at nucleotide position 1019. The tyrosine at codon 340 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001273996 | SCV001457657 | uncertain significance | Fanconi anemia complementation group C | 2020-09-16 | no assertion criteria provided | clinical testing |