Submissions for variant NM_144997.7(FLCN):c.135G>A (p.Ala45=)

gnomAD frequency: 0.00001  dbSNP: rs759930161

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163920	SCV000214515	likely benign	Hereditary cancer-predisposing syndrome	2014-12-10	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.
GeneDx	RCV001697059	SCV000727983	likely benign	not provided	2020-10-15	criteria provided, single submitter	clinical testing
Invitae	RCV000635597	SCV000757016	likely benign	Birt-Hogg-Dube syndrome	2023-11-05	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000635597	SCV001280859	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001122163	SCV001280860	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.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000635597	SCV004015738	likely benign	Birt-Hogg-Dube syndrome	2023-07-07	criteria provided, single submitter	clinical testing