ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2986A>G (p.Thr996Ala)

gnomAD frequency: 0.00010  dbSNP: rs139753238
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001705073 SCV000243683 likely benign not provided 2020-08-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000231299 SCV000285323 benign Tuberous sclerosis 2 2025-01-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV000561234 SCV000675493 benign Hereditary cancer-predisposing syndrome 2020-12-11 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001705073 SCV001477868 uncertain significance not provided 2020-02-18 criteria provided, single submitter clinical testing The TSC2 c.2986A>G; p.Thr996Ala variant (rs139753238), to our knowledge, is not reported in the medical literature but is reported in the ClinVar database (Variation ID: 207738). This variant is found in the African population with an allele frequency of 0.04% (10/24884 alleles) in the Genome Aggregation Database. The threonine at codon 996 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of this variant is uncertain at this time.
Genome-Nilou Lab RCV000231299 SCV002039706 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000561234 SCV002533356 likely benign Hereditary cancer-predisposing syndrome 2021-06-24 criteria provided, single submitter curation
All of Us Research Program, National Institutes of Health RCV003996891 SCV004822163 uncertain significance Tuberous sclerosis syndrome 2024-08-06 criteria provided, single submitter clinical testing This missense variant replaces threonine with alanine at codon 996 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with tuberous sclerosis complex in the literature. This variant has been identified in 10/281666 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Myriad Genetics, Inc. RCV000231299 SCV005404802 likely benign Tuberous sclerosis 2 2024-08-14 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.

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