ClinVar Miner

Submissions for variant NM_003242.6(TGFBR2):c.1085A>G (p.His362Arg)

dbSNP: rs863223842
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000200101 SCV000250932 likely pathogenic not provided 2014-05-20 criteria provided, single submitter clinical testing p.His362Arg (CAC>CGC): c.1085 A>G in exon 4 of the TGFBR2 gene (NM_003242.5)The H362R variant in the TGFBR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The H362R variant is a conservative amino acid substitution as these residues share similar properties, and are least likely to impact secondary structure. However, the H362 residue is conserved across species. In silico analysis predicts H362R is probably damaging to the protein structure/function. Mutations in nearby residues (A355P, R356P, G357R, H360P, K372R) have been reported in association with Loeys Dietz, TAAD or related disorders, further supporting the functional importance of this region of the protein. Furthermore, the H362R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. This variant was found in TAAD
Neuberg Centre For Genomic Medicine, NCGM RCV003338459 SCV004047446 uncertain significance Loeys-Dietz syndrome 2 criteria provided, single submitter clinical testing The c.1085A>G (p.His362Arg) variant has been submitted to ClinVar as a Likely Pathogenic variant, but no details are available for independent assessment. It has not been reported in affected individuals. The p.His362Arg variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid His at position 362 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.His362Arg in TGFBR2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).

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