ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3989C>T (p.Thr1330Met) (rs397515209)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001703964 SCV000243697 likely benign not provided 2021-04-07 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 22490766, 23514105)
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000190025 SCV000540609 uncertain significance not specified 2016-10-20 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 proband with features of TSC and the unaffected parent of a child with autism. ClinVar: VUS by GeneDx (who report they have seen it on their epilepsy panel?)
Invitae RCV000458400 SCV000544529 benign Tuberous sclerosis 2 2020-10-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV000571810 SCV000664598 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-20 criteria provided, single submitter clinical testing The p.T1330M variant (also known as c.3989C>T), located in coding exon 32 of the TSC2 gene, results from a C to T substitution at nucleotide position 3989. The threonine at codon 1330 is replaced by methionine, an amino acid with similar properties. This alteration has been reported in a Korean patient with a definitive diagnosis of tuberous sclerosis complex (TSC) and in the mother of a proband with autism spectrum disorder (ASD), but not in the proband themself (Jang MA et al. Pediatr Neurol. 2012 Apr;46(4):222-4; Bahl S et al. Mol Autism. 2013 Mar 20;4(1):5). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Illumina Clinical Services Laboratory,Illumina RCV000055604 SCV001274388 uncertain significance Tuberous sclerosis syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Tuberous sclerosis database (TSC2) RCV000055507 SCV000083730 not provided Autism spectrum disorder no assertion provided curation
Tuberous sclerosis database (TSC2) RCV000055604 SCV000083829 not provided Tuberous sclerosis syndrome no assertion provided curation

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