ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1661C>T (p.Ser554Leu)

gnomAD frequency: 0.00001  dbSNP: rs45471596
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189986 SCV000243657 uncertain significance not provided 2018-11-19 criteria provided, single submitter clinical testing This variant is denoted TSC2 c.1661C>T at the cDNA level, p.Ser554Leu (S554L) at the protein level, and results in the change of a Serine to a Leucine (TCG>TTG). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. TSC2 Ser554Leu was observed at an allele frequency of 0.02% (5/30,782) in individuals of South Asian ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether TSC2 Ser554Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV001083566 SCV000644270 benign Tuberous sclerosis 2 2023-11-13 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001083566 SCV002039567 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV002256101 SCV002530984 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-01 criteria provided, single submitter curation
Ambry Genetics RCV002256101 SCV002706534 likely benign Hereditary cancer-predisposing syndrome 2022-04-22 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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