Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Diagnostic Laboratory, |
RCV000239703 | SCV000298058 | uncertain significance | Multiple fibrofolliculomas | 2016-07-18 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000489495 | SCV000577487 | pathogenic | not provided | 2018-02-06 | criteria provided, single submitter | clinical testing | This pathogenic variant is denoted FLCN c.763C>T at the cDNA level, p.His255Tyr (H255Y) at the protein level, and results in the change of a Histidine to a Tyrosine (CAC>TAC). This variant has been reported in at least one individual with Birt-Hogg-Dub? syndrome (Hasumi 2016). FLCN His255Tyr demonstrated reduced FLCN protein compared to wild-type in a functional assay and, in a mouse model, FLCN His255Tyr led to the development of an oncocytic hybrid kidney tumor (Hasumi 2009, Hasumi 2016). A missense variant in the same residue (His255Pro) has been reported in association with Birt-Hogg-Dub? syndrome, supporting the functional importance of this region of the protein (Nahorski 2011). FLCN His255Tyr was not observed in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, we consider this variant to be pathogenic. |