ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.992C>T (p.Ser331Phe)

gnomAD frequency: 0.00004  dbSNP: rs202215080
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001019912 SCV001181326 benign Hereditary cancer-predisposing syndrome 2024-03-11 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001346447 SCV001540652 uncertain significance Birt-Hogg-Dube syndrome 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 331 of the FLCN protein (p.Ser331Phe). This variant is present in population databases (rs202215080, gnomAD 0.07%). 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: 823563). 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 not expected to disrupt FLCN protein function with a negative predictive value of 80%. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001800930 SCV002046965 likely benign not provided 2021-04-21 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV004789348 SCV005406240 likely benign Birt-Hogg-Dube syndrome 1 2024-08-29 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.

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