Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001022425 | SCV001184158 | likely benign | Hereditary cancer-predisposing syndrome | 2023-05-10 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Invitae | RCV001298715 | SCV001487779 | uncertain significance | Birt-Hogg-Dube syndrome | 2022-10-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 15 of the FLCN protein (p.Gly15Ser). This variant is present in population databases (rs539468848, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 824865). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FLCN protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Gene |
RCV003318655 | SCV004022725 | uncertain significance | not provided | 2023-07-21 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in an individual with chromophobe renal tumor and family history of renal tumors in published literature (Lagerstedt-Robinson et al., 2022); This variant is associated with the following publications: (PMID: 33726816, 35176117) |
ARUP Laboratories, |
RCV003318655 | SCV004565127 | uncertain significance | not provided | 2023-06-20 | criteria provided, single submitter | clinical testing | The FLCN c.43G>A; p.Gly15Ser variant (rs539468848) is reported in the ClinVar database (Variation ID: 824865). This variant is observed in the general population with an overall allele frequency of 0.004% (11/250194 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is deleterious (REVEL: 0.901). Due to limited information, the clinical significance of this variant is uncertain at this time. |