ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1229T>G (p.Leu410Arg)

dbSNP: rs137854298
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000201010 SCV000255871 likely pathogenic Tuberous sclerosis 2 2015-08-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000201010 SCV000962761 uncertain significance Tuberous sclerosis 2 2022-07-18 criteria provided, single submitter clinical testing This missense change has been observed in individuals with clinical features of tuberous sclerosis complex (PMID: 22903760; Invitae). 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. Experimental studies have shown that this missense change affects TSC2 function (PMID: 22903760). 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. ClinVar contains an entry for this variant (Variation ID: 49680). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 410 of the TSC2 protein (p.Leu410Arg).
Genome-Nilou Lab RCV000201010 SCV002041138 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
GeneDx RCV002468995 SCV002765240 likely pathogenic not provided 2022-12-14 criteria provided, single submitter clinical testing Published functional studies demonstrate that this variant has a damaging affect on TSC1-TSC2 complex formation (Hoogeveen-Westerveld et al., 2013); Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22903760)
Tuberous sclerosis database (TSC2) RCV000042942 SCV000066739 not provided Tuberous sclerosis syndrome no assertion provided curation

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