ClinVar Miner

Submissions for variant NM_004612.4(TGFBR1):c.1121G>A (p.Gly374Glu)

dbSNP: rs1554701930
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000538755 SCV000658841 pathogenic Familial thoracic aortic aneurysm and aortic dissection 2021-05-04 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 374 of the TGFBR1 protein (p.Gly374Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Loeys–Dietz Syndrome (PMID: 16928994, 27879313, Invitae). ClinVar contains an entry for this variant (Variation ID: 477551). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TGFBR1 protein function. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001578258 SCV001805812 uncertain significance not provided 2020-11-23 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27879313, 17061023, 16928994)

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