Submissions for variant NM_003242.6(TGFBR2):c.999A>G (p.Leu333=)

gnomAD frequency: 0.02537  dbSNP: rs2229102

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037740	SCV000061402	benign	not specified	2007-04-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000037740	SCV000168939	benign	not specified	2013-04-15	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.
PreventionGenetics, part of Exact Sciences	RCV000037740	SCV000309523	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000248566	SCV000317399	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-09-09	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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	RCV000393230	SCV000442868	benign	Marfan syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000303261	SCV000442869	benign	Loeys-Dietz syndrome 2	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 Laboratory Services, Illumina	RCV000248566	SCV000442870	benign	Familial thoracic aortic aneurysm and aortic dissection	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000248566	SCV000559160	benign	Familial thoracic aortic aneurysm and aortic dissection	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587320	SCV000698200	benign	not provided	2016-04-07	criteria provided, single submitter	clinical testing	Variant summary: The c.999A>G variant affects a non-conserved nucleotide, resulting in no amino acid change. One in-silico tool predicts damaging outcome for this variant. 5/5 splice-site tools via Alamut predict that this variant does not affect normal splicing. However, these predictions are not confirmed by experimental studies. This variant is found in 926/121218 control chromosomes (including 32 homozygotes) at a frequency of 0.0076391, which is about 1630 times greater than the maximal expected frequency of a pathogenic allele (0.0000047) in this gene, suggesting this variant is benign. In addition, multiple clinical laboratories classified this variant as benign. Taken together, this variant has been classified as Benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000248566	SCV000901784	benign	Familial thoracic aortic aneurysm and aortic dissection	2016-06-19	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000248566	SCV000910834	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-15	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587320	SCV001158638	benign	not provided	2023-10-17	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277127	SCV002566165	benign	Ehlers-Danlos syndrome	2022-02-17	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000037740	SCV001807705	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000037740	SCV001975908	benign	not specified		no assertion criteria provided	clinical testing