ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.3080G>A (p.Arg1027Gln) (rs796053461)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189857 SCV000243510 uncertain significance not specified 2014-03-05 criteria provided, single submitter clinical testing p.Arg1027Gln (R1027Q) CGG>CAG: c.3080 G>A in exon 23 of the TSC1 gene (NM_000368.4). The R1027Q variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It 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 R1027Q 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 well conserved across species. However, the vast majority of TSC1 mutations result in protein truncation, while missense mutations have been reported only rarely (Northrup et al., 2011; Au et al., 2007). Additionally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.The presence of R1027Q in this parent who has a history of seizures does not clarify whether this variant is a disease-causing mutation or a benign variant. Therefore, based on the currently available information, it is unclear whether R1027Q is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000233178 SCV000284714 likely benign not provided 2019-02-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV000561979 SCV000675424 uncertain significance Hereditary cancer-predisposing syndrome 2015-10-23 criteria provided, single submitter clinical testing

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