Submissions for variant NM_144997.7(FLCN):c.397-14C>T

gnomAD frequency: 0.40309  dbSNP: rs1736219

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000082638	SCV000114680	benign	not specified	2017-04-10	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000082638	SCV000198125	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	397-14C>T in intron 5 of FLCN: This variant is not expected to have clinical sig nificance because it has been identified in 48.5% (4163/8588) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs1736219).
PreventionGenetics, part of Exact Sciences	RCV000082638	SCV000316056	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000353310	SCV000401021	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.
Illumina Laboratory Services, Illumina	RCV000277303	SCV000401022	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589883	SCV000699933	benign	not provided	2016-05-04	criteria provided, single submitter	clinical testing	Variant summary: The FLCN variant, c.397-14C>T is located at a non-conserved intronic position, not widely known to affect splicing, with 5/5 in silico programs via Alamut predicting no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest is observed in the large, broad control population, ExAC, with an allele frequency of 20124/41572 (1/2 including 4822 homozygotes), which significantly exceeds the estimated maximum expected allele frequency for a pathogenic FLCN variant of 1/769230. The variant of interest has also been reported by multiple reputable clinical laboratories as "benign." Therefore, the variant of interest has been classified as Benign.
GeneDx	RCV000589883	SCV001759143	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000277303	SCV001933499	benign	Birt-Hogg-Dube syndrome	2021-08-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000353310	SCV001933500	benign	Familial spontaneous pneumothorax	2021-08-10	criteria provided, single submitter	clinical testing
Invitae	RCV000277303	SCV002488727	benign	Birt-Hogg-Dube syndrome	2024-02-01	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000277303	SCV004015730	benign	Birt-Hogg-Dube syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000082638	SCV001928008	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000082638	SCV001952980	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000082638	SCV001971897	benign	not specified		no assertion criteria provided	clinical testing