ClinVar Miner

Submissions for variant NM_004612.4(TGFBR1):c.220G>A (p.Glu74Lys)

gnomAD frequency: 0.00001  dbSNP: rs998268148
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000654807 SCV000776707 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 74 of the TGFBR1 protein (p.Glu74Lys). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TGFBR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 543903). 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 not expected to disrupt TGFBR1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen RCV000999188 SCV001155687 uncertain significance not provided 2019-02-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000654807 SCV001340991 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-08-22 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 74 of the TGFBR1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/250892 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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