ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1070C>T (p.Ala357Val) (rs150195368)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000122202 SCV000205284 likely benign not specified 2020-07-01 criteria provided, single submitter clinical testing The p.Ala357Val variant in TSC2 has been reported in 2 individuals with Tuberous Sclerosis-2 (Peron 2018 PMID: 29432982). It has also been identified in 0.092% (23/25098) (1 homozygote) Finnish chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 41724). Functional studies indicate that this variant may not impact protein function (Hoogevenn-Westerveld 2011 PMID: 21309039). However, this in vitro assay may not accurately represent biological function. In addition, computational prediction tools and conservation analysis suggest that the Ala357Val variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of this variant is uncertain, its frequency suggests that it is more likely to be benign. ACMG/AMP Criteria applied: PS4_Moderate, BS1_Supporting.
Ambry Genetics RCV000163628 SCV000214196 benign Hereditary cancer-predisposing syndrome 2015-11-19 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Intact protein function observed in appropriate functional assay(s);Other data supporting benign classification
Invitae RCV000230505 SCV000285220 benign Tuberous sclerosis 2 2020-12-07 criteria provided, single submitter clinical testing
GeneDx RCV000034641 SCV000515014 benign not provided 2020-06-09 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 21309039, 22703879, 23514105, 24728327, 22558107, 25801821, 24356096, 24631838, 22885699, 26580448, 29432982)
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000122202 SCV000702129 likely benign not specified 2016-10-31 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000230505 SCV000845562 uncertain significance Tuberous sclerosis 2 2018-08-07 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000714826 SCV000845563 uncertain significance Focal cortical dysplasia type II 2018-08-07 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000034641 SCV001150684 likely benign not provided 2021-05-01 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034641 SCV000043524 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Tuberous sclerosis database (TSC2) RCV000055595 SCV000083820 not provided Tuberous sclerosis syndrome no assertion provided curation
ITMI RCV000122202 SCV000086422 not provided not specified 2013-09-19 no assertion provided reference population
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000034641 SCV001800689 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000034641 SCV001921010 likely benign not provided no assertion criteria provided clinical testing

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