ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.3890A>G (p.Glu1297Gly) (rs200342067)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181499 SCV000233802 uncertain significance not specified 2016-02-29 criteria provided, single submitter clinical testing The Glu1297Gly variant in the FBN1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Glu1297Gly results in a non-conservative amino acid substitution of a negatively-charged Glutamic acid with a non-polar Glycine at a position that is highly conserved across species. In silico analysis predicts Glu1297Gly is damaging to the protein structure/function. Mutations in nearby residues (Cys1284Tyr, Lys1300Glu) have been reported in association with Marfan syndrome/TAAD, further supporting the functional importance of this region of the protein. Glu1297Gly was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, however it was observed in 0.3% of Americans in the 1000 Genomes database. With the clinical and molecular information available at this time, we cannot definitively determine if Glu1297Gly in the FBN1 gene is a disease-causing mutation or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000273225 SCV000392386 benign Acromicric dysplasia 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.
Illumina Clinical Services Laboratory,Illumina RCV000328328 SCV000392387 benign Weill-Marchesani 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.
Illumina Clinical Services Laboratory,Illumina RCV000378194 SCV000392388 benign Stiff skin 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.
Illumina Clinical Services Laboratory,Illumina RCV000264838 SCV000392389 benign Geleophysic dysplasia 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.
Illumina Clinical Services Laboratory,Illumina RCV000324811 SCV000392390 likely benign Familial thoracic aortic aneurysm and aortic dissection 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 Clinical Services Laboratory,Illumina RCV000379285 SCV000392391 benign Ectopia lentis, isolated, autosomal dominant 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.
Illumina Clinical Services Laboratory,Illumina RCV000279942 SCV000392392 benign Marfan 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.
Invitae RCV001084524 SCV000557063 benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588770 SCV000695527 likely benign not provided 2016-10-24 criteria provided, single submitter clinical testing Variant summary: The FBN1 c.3890A>G (p.Glu1297Gly) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 102/121364 control chromosomes (2 homozygotes), predominantly observed in the Latino subpopulation at a frequency of 0.0085625 (99/11562). This frequency is about 76 times the estimated maximal expected allele frequency of a pathogenic FBN1 variant (0.0001125), suggesting this is possibly a benign polymorphism found primarily in the populations of Latino origin. This variant has been reported in two patients without strong evidience of causality. One clinical diagnostic laboratory classified this variant as uncertain significance. Taken together, this variant is classified as likely benign until more evidence becomes available.
Ambry Genetics RCV000620106 SCV000739795 benign Cardiovascular phenotype 2018-08-22 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Color RCV000324811 SCV001359742 benign Familial thoracic aortic aneurysm and aortic dissection 2018-03-16 criteria provided, single submitter clinical testing

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