Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000234528 | SCV000287923 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2023-09-19 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000234528 | SCV001349246 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2020-07-22 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001526891 | SCV001737637 | likely benign | not specified | 2021-05-24 | criteria provided, single submitter | clinical testing | Variant summary: TGFBR2 c.4G>T (p.Gly2Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.9e-05 in 219764 control chromosomes, predominantly at a frequency of 0.00064 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 205 fold of the estimated maximal expected allele frequency for a pathogenic variant in TGFBR2 causing Loeys-Dietz Syndrome phenotype (3.1e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.4G>T in individuals affected with Loeys-Dietz Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |
Gene |
RCV002259326 | SCV002538701 | uncertain significance | not provided | 2022-06-22 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function |
Ambry Genetics | RCV000234528 | SCV002640744 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-07-08 | criteria provided, single submitter | clinical testing | The p.G2C variant (also known as c.4G>T), located in coding exon 1 of the TGFBR2 gene, results from a G to T substitution at nucleotide position 4. The glycine at codon 2 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |