Submissions for variant NM_144997.7(FLCN):c.268G>T (p.Ala90Ser)

gnomAD frequency: 0.00029  dbSNP: rs141140415

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000227232	SCV000291441	likely benign	Birt-Hogg-Dube syndrome	2024-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000034791	SCV000321651	likely benign	not provided	2020-08-31	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24728327, 26096009, 22703879, 27734835)
Illumina Laboratory Services, Illumina	RCV000332283	SCV000401023	uncertain significance	Familial spontaneous pneumothorax	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000227232	SCV000401024	benign	Birt-Hogg-Dube syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Ambry Genetics	RCV000571977	SCV000673406	likely benign	Hereditary cancer-predisposing syndrome	2018-05-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034791	SCV001477789	uncertain significance	not provided	2023-10-09	criteria provided, single submitter	clinical testing	The FLCN c.268G>T; p.Ala90Ser variant (rs141140415), has not been reported in the medical literature in FLCN-related conditions, but is reported in the ClinVar database (Variation ID: 41857). This variant is found in the general population with an overall allele frequency of 0.03% (97/282,776 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.448). Due to limited information, the clinical significance of this variant is uncertain at this time.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000034791	SCV002009876	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000571977	SCV002530133	uncertain significance	Hereditary cancer-predisposing syndrome	2021-04-20	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000121101	SCV002760908	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000034791	SCV004219717	benign	not provided	2022-11-17	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000034791	SCV005412679	uncertain significance	not provided	2023-10-17	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034791	SCV000043271	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.
ITMI	RCV000121101	SCV000085269	not provided	not specified	2013-09-19	no assertion provided	reference population
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000034791	SCV001808015	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000034791	SCV001954528	likely benign	not provided		no assertion criteria provided	clinical testing