Submissions for variant NM_144997.7(FLCN):c.586A>G (p.Ile196Val) (rs201078144)

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	uncertain significance	Hereditary cancer-predisposing syndrome	2018-08-10	criteria provided, single submitter	clinical testing	Insufficient or conflicting evidence
Biesecker Lab/Clinical Genomics Section,National Institutes of Health	RCV000034793	SCV000043269	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.