ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.538C>G (p.Leu180Val) (rs45485591)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000043112 SCV000395560 uncertain significance Tuberous sclerosis syndrome 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000419036 SCV000528122 likely benign not specified 2018-02-19 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000539140 SCV000644643 uncertain significance Tuberous sclerosis 2 2018-04-03 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 180 of the TSC2 protein (p.Leu180Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs45485591, ExAC 0.001%). This variant has been reported in an individual with tuberous sclerosis in the Leiden Open-source Variation Database (PMID: 21520333). However, in that individual a pathogenic deletion was also identified in TSC2 which suggests that this c.538C>G variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 49846). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000729019 SCV000856652 uncertain significance not provided 2017-09-14 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000043112 SCV000066911 not provided Tuberous sclerosis syndrome no assertion provided curation
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000781951 SCV000920395 uncertain significance Seizures 2016-12-19 no assertion criteria provided clinical testing

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