ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.3278G>A (p.Arg1093Gln) (rs550526986)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724617 SCV000228009 uncertain significance not provided 2015-03-13 criteria provided, single submitter clinical testing
GeneDx RCV000724617 SCV000531940 uncertain significance not provided 2017-12-04 criteria provided, single submitter clinical testing The de novo R1093Q variant in the TSC1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R1093Q 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. The R1093Q variant 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 that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R1093Q as a variant of uncertain significance.
Invitae RCV000642039 SCV000763692 uncertain significance Tuberous sclerosis 1 2019-07-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1093 of the TSC1 protein (p.Arg1093Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs550526986, ExAC 0.006%). This variant has been reported in an individual affected with bilateral keratoconus (PMID: 29261847). ClinVar contains an entry for this variant (Variation ID: 195727). 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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