ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.577G>T (p.Glu193Ter)

dbSNP: rs45517112
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003485532 SCV004296634 pathogenic Tuberous sclerosis 2 2023-02-14 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with TSC2-related conditions. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 50039). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu193*) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050).
GeneDx RCV005089399 SCV005848910 pathogenic not provided 2024-08-13 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25525159, 37937776)
Tuberous sclerosis database (TSC2) RCV000043305 SCV000067111 not provided Tuberous sclerosis syndrome no assertion provided curation
deCODE genetics, Amgen RCV003485532 SCV004022275 likely pathogenic Tuberous sclerosis 2 2023-07-21 no assertion criteria provided research The variant NM_000548.5:c.577G>T (chr16:2055497) in TSC2 was detected in 1 heterozygote out of 58K WGS Icelanders (MAF= 0,001%). This variant has been reported in ClinVar previously, but a clinical significance interpretation was not provided. Based on ACMG criteria (PVS1, PM2) this variant classifies as likely pathogenic.

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