ClinVar Miner

Submissions for variant NM_003239.5(TGFB3):c.1001A>G (p.His334Arg)

dbSNP: rs1021920873
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002544872 SCV000818026 uncertain significance Rienhoff syndrome 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 334 of the TGFB3 protein (p.His334Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with TGFB3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly 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.
Ambry Genetics RCV002369854 SCV002685947 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-10-14 criteria provided, single submitter clinical testing The p.H334R variant (also known as c.1001A>G), located in coding exon 6 of the TGFB3 gene, results from an A to G substitution at nucleotide position 1001. The histidine at codon 334 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003403600 SCV004103396 uncertain significance TGFB3-related disorder 2022-10-13 criteria provided, single submitter clinical testing The TGFB3 c.1001A>G variant is predicted to result in the amino acid substitution p.His334Arg. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
GeneDx RCV004760710 SCV005369223 uncertain significance not provided 2023-07-12 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function

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