Submissions for variant NM_000138.5(FBN1):c.3442C>G (p.Pro1148Ala)

gnomAD frequency: 0.01315  dbSNP: rs140598

Total submissions: 24

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035172	SCV000058814	benign	not specified	2021-08-13	criteria provided, single submitter	clinical testing	The p.Pro1148Ala variant in FBN1 is classified as benign because it has been identified in 24% (4787/19944) of East Asian chromosomes, including 593 homozygotes, by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1.
GeneDx	RCV000035172	SCV000169888	benign	not specified	2013-03-08	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.
CSER _CC_NCGL, University of Washington	RCV000029726	SCV000212200	benign	Marfan syndrome	2015-03-11	criteria provided, single submitter	research
Eurofins Ntd Llc (ga)	RCV000035172	SCV000228594	benign	not specified	2014-06-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000035172	SCV000302550	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000770675	SCV000317325	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-02-19	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Illumina Laboratory Services, Illumina	RCV000029726	SCV000392442	benign	Marfan syndrome	2018-03-06	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000461828	SCV000557058	benign	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2024-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811206	SCV000603605	benign	not provided	2023-11-27	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770675	SCV000902136	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-10-03	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000770675	SCV000902605	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001118162	SCV001276426	benign	Weill-Marchesani syndrome	2018-03-06	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	RCV000770675	SCV001278140	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-06	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	RCV001119710	SCV001278141	benign	Stiff skin syndrome	2018-03-06	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	RCV001119711	SCV001278142	benign	Geleophysic dysplasia	2018-03-06	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	RCV001119712	SCV001278143	benign	Ectopia lentis 1, isolated, autosomal dominant	2018-03-06	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	RCV001119713	SCV001278144	benign	Acromicric dysplasia	2018-03-06	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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002276585	SCV002566525	benign	Connective tissue disorder	2022-07-14	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000029726	SCV004814807	benign	Marfan syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001811206	SCV005295675	benign	not provided		criteria provided, single submitter	not provided
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000029726	SCV000052379	benign	Marfan syndrome	2013-03-12	no assertion criteria provided	clinical testing
OMIM	RCV000030812	SCV000053483	benign	FNB1 POLYMORPHISM	1997-05-01	no assertion criteria provided	literature only
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000035172	SCV001798210	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000035172	SCV001807589	benign	not specified		no assertion criteria provided	clinical testing