Submissions for variant NM_004612.4(TGFBR1):c.191A>G (p.Lys64Arg)

dbSNP: rs886042300

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000320806	SCV000333241	uncertain significance	not provided	2015-08-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001166107	SCV001328442	uncertain significance	Loeys-Dietz syndrome 1	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, 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.
Ambry Genetics	RCV002411148	SCV002721407	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2022-05-18	criteria provided, single submitter	clinical testing	The p.K64R variant (also known as c.191A>G), located in coding exon 2 of the TGFBR1 gene, results from an A to G substitution at nucleotide position 191. The lysine at codon 64 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV002411148	SCV003460245	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-04-16	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with TGFBR1-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 282059). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 64 of the TGFBR1 protein (p.Lys64Arg).
Color Diagnostics, LLC DBA Color Health	RCV002411148	SCV004362440	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-11-22	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with arginine at codon 64 of the TGFBR1 protein. Computational prediction suggests that this variant may have a neutral impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TGFBR1-related disorders in the literature. This variant has not been identified 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.