ClinVar Miner

Submissions for variant NM_004612.4(TGFBR1):c.1117G>A (p.Val373Met) (rs1554701926)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000588447 SCV000698481 uncertain significance not provided 2017-03-21 criteria provided, single submitter clinical testing Variant summary: The TGFBR1 c.1117G>A (p.Val373Met) variant located in the protein kinase-like domain (via InterPro) involves the alteration of a conserved nucleotide and 3/4 in silico tools (SNPs&GO not captured due to low reliability index) predict a damaging outcome, although these predictions have yet to be functionally assessed. for this variant. This variant is absent from the large control database ExAC (0/121100 control chromosomes). To our knowledge, the variant of interest has not been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories, nor has it been evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.
Invitae RCV000654812 SCV000776712 uncertain significance Thoracic aortic aneurysm and aortic dissection 2017-12-27 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 373 of the TGFBR1 protein (p.Val373Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TGFBR1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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