Submissions for variant NM_144997.7(FLCN):c.726A>T (p.Thr242=)

gnomAD frequency: 0.02907  dbSNP: rs113938514

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000082641	SCV000114683	benign	not specified	2013-04-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000129668	SCV000184466	benign	Hereditary cancer-predisposing syndrome	2014-06-26	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000082641	SCV000269116	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	Thr242Thr in exon 7 of FLCN: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 5.4% (239/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs113938514).
PreventionGenetics, part of Exact Sciences	RCV000082641	SCV000316058	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000384438	SCV000401010	benign	Birt-Hogg-Dube syndrome	2018-01-12	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.
Illumina Laboratory Services, Illumina	RCV000290141	SCV000401011	benign	Familial spontaneous pneumothorax	2018-01-12	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.
Invitae	RCV000384438	SCV000560336	benign	Birt-Hogg-Dube syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586027	SCV000699934	benign	not provided	2016-05-04	criteria provided, single submitter	clinical testing	Variant summary: The c.726A>T (p.Thr242Thr) variant in FLCN affects a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice-tools in Alamut predict no significant effect on splicing, although these predictions have yet to be confirmed by functional studies. This variant is found in 2446/121198 control chromosomes (42 homozygotes) at a frequency of 0.02018, which greatly exceeds maximal expected frequency of a pathogenic allele (0.0000013), strong evidence that this variant is benign. In addition, multiple reputable clinical laboratories have classified this variant as benign. Taken together, this variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000586027	SCV001472064	benign	not provided	2023-11-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000586027	SCV001944071	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000586027	SCV002047262	benign	not provided	2021-03-30	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000082641	SCV002551354	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000384438	SCV004015725	benign	Birt-Hogg-Dube syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000082641	SCV001807503	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000082641	SCV001928422	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000082641	SCV001953529	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000082641	SCV002037009	benign	not specified		no assertion criteria provided	clinical testing