ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.170G>A (p.Arg57His) (rs397514949)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000472366 SCV000544328 uncertain significance Tuberous sclerosis 2 2018-11-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 57 of the TSC2 protein (p.Arg57His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs397514949, ExAC 0.002%). This variant has been reported in several individuals from a single family with apparently mild features of tuberous sclerosis complex in the Leiden Open-source Variation Database (PMID: 21520333). The clinical significance of this observation in uncertain. ClinVar contains an entry for this variant (Variation ID: 64932). Experimental studies have shown that this  missense change results in both reduced TSC2 and TSC1 protein levels, suggesting that the stable TSC1-TSC2 (hamartin-tuberin) complex is disrupted, and impairs the ability of this complex to inhibit TORC1 kinase (PMID: 21309039). 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.
Tuberous sclerosis database (TSC2) RCV000055135 SCV000083353 not provided Tuberous sclerosis syndrome no assertion provided curation

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