ClinVar Miner

Submissions for variant NM_000545.6(HNF1A):c.599G>A (p.Arg200Gln) (rs893256143)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000424339 SCV000521026 likely pathogenic not provided 2016-06-09 criteria provided, single submitter clinical testing The R200Q variant in the HNF1A gene has been published previosuly in association with MODY (Toaima et al., 2005; Tatsi et al., 2013; Chambers et al., 2015). The 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. R200Q is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position within the DNA-binding domain and within a nuclear localization signal that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In the absence of functional studies, the actual effect of this missense change is unknown. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Athena Diagnostics Inc RCV000424339 SCV000613622 pathogenic not provided 2019-03-15 criteria provided, single submitter clinical testing The best available variant frequency is uninformative because there are too few occurrences in population data. Statistically enriched in patients compared to ethnically matched controls (p<0.0001). Found in symptomatic patients. Predicted to have a damaging effect on the protein. One other pathogenic or likely pathogenic variant affects the same amino acid. Damaging to protein function(s) relevant to disease mechanism.
Constantin Polychronakos Laboratory,The Research Institute of the McGill University Health Centre RCV001175316 SCV001250630 pathogenic Diabetes mellitus no assertion criteria provided research PS1 PM2 PM5 PP3 PP5

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