ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.952G>A (p.Glu318Lys)

gnomAD frequency: 0.00003  dbSNP: rs756787389
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000635565 SCV000756982 uncertain significance Birt-Hogg-Dube syndrome 2024-11-18 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 318 of the FLCN protein (p.Glu318Lys). This variant is present in population databases (rs756787389, 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: 530001). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV001019466 SCV001180828 benign Hereditary cancer-predisposing syndrome 2024-02-09 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.
Fulgent Genetics, Fulgent Genetics RCV005004291 SCV002812856 uncertain significance Familial spontaneous pneumothorax; Nonpapillary renal cell carcinoma; Colorectal cancer; Birt-Hogg-Dube syndrome 1 2024-04-25 criteria provided, single submitter clinical testing
GeneDx RCV003238793 SCV003936631 uncertain significance not provided 2022-12-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Myriad Genetics, Inc. RCV004788054 SCV005406332 likely benign Birt-Hogg-Dube syndrome 1 2024-08-30 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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