Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000464556 | SCV000549447 | uncertain significance | Multiple fibrofolliculomas | 2020-01-09 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with valine at codon 196 of the FLCN protein (p.Ile196Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs201078144, ExAC 0.002%). This variant has not been reported in the literature in individuals with FLCN-related disease. ClinVar contains an entry for this variant (Variation ID: 41859). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Ambry Genetics | RCV001024623 | SCV001186669 | likely benign | Hereditary cancer-predisposing syndrome | 2020-09-03 | criteria provided, single submitter | clinical testing | In silico models in agreement (benign);Other data supporting benign classification |
Biesecker Lab/Clinical Genomics Section, |
RCV000034793 | SCV000043269 | variant of unknown significance | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Uncertain significance. |