Submissions for variant NM_004612.4(TGFBR1):c.457G>A (p.Val153Ile)

gnomAD frequency: 0.00115  dbSNP: rs56014374

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001580027	SCV000250872	likely benign	not provided	2021-06-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25715477, 28655553, 34032567, 30809044)
PreventionGenetics, part of Exact Sciences	RCV000200131	SCV000310512	likely benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000251582	SCV000319698	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-07-25	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.
Illumina Laboratory Services, Illumina	RCV000292925	SCV000475615	likely benign	Loeys-Dietz syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000349783	SCV000475616	likely benign	Loeys-Dietz syndrome 1	2018-02-01	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000251582	SCV000475617	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000251582	SCV000559247	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2024-01-31	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000251582	SCV000782357	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-11-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000251582	SCV000902962	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-16	criteria provided, single submitter	clinical testing
Mendelics	RCV000349783	SCV001137880	likely benign	Loeys-Dietz syndrome 1	2019-05-28	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000251582	SCV001333559	benign	Familial thoracic aortic aneurysm and aortic dissection	2017-11-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001580027	SCV002564056	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	TGFBR1: BP4, BS1
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277548	SCV002566139	benign	Ehlers-Danlos syndrome	2022-06-27	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003227711	SCV003924164	likely benign	Loeys-Dietz syndrome 1; Multiple self-healing squamous epithelioma	2021-03-30	criteria provided, single submitter	clinical testing	TGFBR1 NM_004612.3 exon 3 p.Val153Ile (c.457G>A): This variant has been reported in the literature in one individual with vascular anomalies (Mattassi 2018 PMID:28655553). However, this variant is present in 0.1% (129/64576) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/9-99132622-G-A?dataset=gnomad_r3) and is present in ClinVar, with several labs classifying this variant as benign or likely benign (Variation ID:213868). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease, but requires further evidence. Therefore this variant is classified as likely benign.
All of Us Research Program, National Institutes of Health	RCV000292925	SCV004840381	likely benign	Loeys-Dietz syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001580027	SCV005224726	likely benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001580027	SCV001809423	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001580027	SCV001965753	likely benign	not provided		no assertion criteria provided	clinical testing