ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4355C>T (p.Ser1452Leu) (rs45517339)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000190032 SCV000243705 uncertain significance not provided 2014-04-02 criteria provided, single submitter clinical testing p.Ser1452Leu (TCG>TTG): c.4355 C>T in exon 34 of the TSC2 gene (NM_000548.3) The S1452L variant was previously reported as S1453L and was considered a benign polymorphism, although no additional information was provided (Au et al., 2007). According to the TSC2 LOVD Variant Database, it was identified in a patient with clinical features of tuberous sclerosis but was also identified in an unaffected parent. 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 S1452L 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. This substitution occurs at a position that is conserved across species. However, this substitution does not occur within known functional domains of the tuberin protein, where many pathogenic missense mutations have been identified (Northrup et al., 2011; Au et al., 2007). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The variant is found in EPILEPSY panel(s).
Invitae RCV001088217 SCV000544375 likely benign Tuberous sclerosis 2 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001022345 SCV001184070 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-14 criteria provided, single submitter clinical testing Insufficient evidence
CeGaT Praxis fuer Humangenetik Tuebingen RCV000190032 SCV001248122 uncertain significance not provided 2019-11-01 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000043095 SCV000066894 not provided Tuberous sclerosis syndrome no assertion provided curation

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