Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166127 | SCV000216898 | likely benign | Hereditary cancer-predisposing syndrome | 2014-10-09 | criteria provided, single submitter | clinical testing | In silico models in agreement (benign);Does not segregate with disease in family study (genes with incomplete penetrance);Intact protein function observed in appropriate functional assay(s) |
| Invitae | RCV000231168 | SCV000291425 | uncertain significance | Multiple fibrofolliculomas | 2019-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with isoleucine at codon 400 of the FLCN protein (p.Val400Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs148257120, ExAC 0.01%). This variant has been reported in individuals affected with Birt-Hogg-Dub (BHD) (PMID: 25519458, 19802896) and renal cell carcinoma (PMID: 28891800), as well as in unaffected individuals (PMID: 24728327). Currently there is insufficient evidence to conclude whether this variant segregates with disease or not. ClinVar contains an entry for this variant (Variation ID: 134431). Experimental studies have shown that this missense change does not disrupt the stability of the folliculin protein, interfere with intracellular localization of folliculin, or impair tumor suppressor activity of the folliculin protein (PMID: 21538689). 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. |
| ITMI | RCV000121111 | SCV000085279 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |