ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.3250T>C (p.Ser1084Pro) (rs796053463)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189862 SCV000243515 uncertain significance not provided 2013-06-27 criteria provided, single submitter clinical testing p.Ser1084Pro (TCA>CCA): c.3250 T>C in exon 23 of the TSC1 gene (NM_000368.3). The Ser1084Pro missense change 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. Ser1084Pro is a non-conservative amino acid substitution as a polar Serine is replaced by a non-polar Proline, and the addition of a bulky Proline may alter the secondary structure of the protein. Ser1084Pro alters a position that is conserved through mammals but is not conserved in more distant species. 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). Multiple in silico algorithms predict that Ser1084Pro is possibly benign, although another model predicts that it may be damaging to the structure/function of the TSC1 protein. Therefore, based on the currently available information, it is unclear whether Ser1084Pro is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).

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