ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.365T>C (p.Met122Thr) (rs796053454)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189834 SCV000243487 uncertain significance not provided 2014-03-03 criteria provided, single submitter clinical testing p.Met122Thr (ATG>ACG): c.365 T>C in exon 6 of the TSC1 gene (NM_000368.4). The Met122Thr 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 Met122Thr variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species and Threonine is observed at this position in other species. In silico analysis predicts this variant likely does not alter the protein structure/function. Additionally, 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). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).

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