ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.977C>T (p.Pro326Leu) (rs138031155)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000264762 SCV000401002 benign Multiple fibrofolliculomas 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 Clinical Services Laboratory,Illumina RCV000319945 SCV000401003 uncertain significance Pneumothorax, primary spontaneous 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, 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.
Invitae RCV000264762 SCV000549441 likely benign Multiple fibrofolliculomas 2019-12-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000567800 SCV000664606 likely benign Hereditary cancer-predisposing syndrome 2018-10-08 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Integrated Genetics/Laboratory Corporation of America RCV000589923 SCV000699936 likely benign not provided 2016-08-31 criteria provided, single submitter clinical testing Variant summary: The FLCN c.977C>T (p.Pro326Leu) variant involves the alteration of a non-conserved nucleotide. 4/5 in silico tools predict a benign outcome for this variant. This variant was found in 22/121304 control chromosomes at a frequency of 0.0001814, which is approximately 145 times the estimated maximal expected allele frequency of a pathogenic FLCN variant (0.0000013), suggesting this variant is likely a benign polymorphism. However, only 22 allele carriers were reported in this dataset, which is not a large enough number to definitively classify this variant as benign in the absence of other information. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely benign.
GeneDx RCV000613024 SCV000728439 likely benign not specified 2018-01-18 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000589923 SCV001334828 uncertain significance not provided 2020-02-01 criteria provided, single submitter clinical testing

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