ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1981G>C (p.Gly661Arg)

dbSNP: rs137854168
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001852893 SCV002256272 uncertain significance Tuberous sclerosis 2 2023-10-11 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 661 of the TSC2 protein (p.Gly661Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of tuberous sclerosis complex (PMID: 22903760). ClinVar contains an entry for this variant (Variation ID: 49697). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC2 protein function. Experimental studies have shown that this missense change does not substantially affect TSC2 function (PMID: 22903760). 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.
GeneDx RCV002291552 SCV002584233 uncertain significance not provided 2022-04-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate no damaging effect: variant does not significantly disrupt the function of the TSC1-TSC2 complex (Hoogeveen-Westerveld 2013); This variant is associated with the following publications: (PMID: 22903760)
Tuberous sclerosis database (TSC2) RCV000042960 SCV000066757 not provided Tuberous sclerosis syndrome no assertion provided curation

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