Submissions for variant NM_003242.6(TGFBR2):c.69G>T (p.Thr23=)

gnomAD frequency: 0.00004  dbSNP: rs878854612

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000234500	SCV000287926	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2024-10-26	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001149561	SCV001310520	uncertain significance	Loeys-Dietz syndrome 2	2018-03-23	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.
Color Diagnostics, LLC DBA Color Health	RCV000234500	SCV001349900	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2019-02-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001582774	SCV001819487	likely benign	not provided	2019-08-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000234500	SCV002665686	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2019-04-19	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.
All of Us Research Program, National Institutes of Health	RCV001149561	SCV004843410	likely benign	Loeys-Dietz syndrome 2	2023-12-13	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV004020798	SCV005016394	likely benign	Diabetic retinopathy		criteria provided, single submitter	research	Potent mutations in TGFBR2 gene encodes the transforming growth factor that have been associated with angiogenesis and diabetic retinopathy. More clinical studies are needed for stronger association. However, more evidence is required to confer the association of this particular variant rs878854612 with diabetic retinopathy.
PreventionGenetics, part of Exact Sciences	RCV003937900	SCV004763160	likely benign	TGFBR2-related disorder	2021-09-24	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).