Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000483167 | SCV000570194 | uncertain significance | not provided | 2018-12-10 | criteria provided, single submitter | clinical testing | This variant is denoted FANCC c.551C>T at the cDNA level, p.Ser184Leu (S184L) at the protein level, and results in the change of a Serine to a Leucine (TCA>TTA). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. FANCC Ser184Leu was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located within the region of interaction with GRP94 and Hsp70 (Gordon 2000). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether FANCC Ser184Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Invitae | RCV001063298 | SCV001228136 | uncertain significance | Fanconi anemia | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with leucine at codon 184 of the FANCC protein (p.Ser184Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs746367952, 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: 421100). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
Natera, |
RCV001063298 | SCV002081249 | uncertain significance | Fanconi anemia | 2018-11-04 | no assertion criteria provided | clinical testing |