ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1492G>A (p.Glu498Lys)

gnomAD frequency: 0.00001  dbSNP: rs45517178
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189888 SCV000243544 likely benign not specified 2013-07-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV001853090 SCV002175985 benign Tuberous sclerosis 2 2023-05-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV002390202 SCV002698750 likely benign Hereditary cancer-predisposing syndrome 2021-04-19 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000189888 SCV003929062 uncertain significance not specified 2023-04-27 criteria provided, single submitter clinical testing Variant summary: TSC2 c.1492G>A (p.Glu498Lys) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251330 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1492G>A in individuals affected with Tuberous Sclerosis Complex has been reported. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (example: Hoogeveen-Westerveld_2013). The following publication has been ascertained in the context of this evaluation (PMID: 22903760). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Mayo Clinic Laboratories, Mayo Clinic RCV003480048 SCV004227493 uncertain significance not provided 2022-11-15 criteria provided, single submitter clinical testing BS3_supporting
Tuberous sclerosis database (TSC2) RCV000055190 SCV000083408 not provided Tuberous sclerosis syndrome no assertion provided curation

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