ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.670G>A (p.Ala224Thr)

dbSNP: rs772558666
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000528200 SCV000644656 likely benign Tuberous sclerosis 2 2024-12-12 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003237914 SCV002011316 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000528200 SCV002041087 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV002255451 SCV002534090 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-18 criteria provided, single submitter curation
Ambry Genetics RCV002255451 SCV002666741 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-19 criteria provided, single submitter clinical testing The p.A224T variant (also known as c.670G>A), located in coding exon 7 of the TSC2 gene, results from a G to A substitution at nucleotide position 670. The alanine at codon 224 is replaced by threonine, an amino acid with similar properties. This variant has been detected in multiple individuals with no reported features of Tuberous sclerosis complex (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
All of Us Research Program, National Institutes of Health RCV003999333 SCV004816997 uncertain significance Tuberous sclerosis syndrome 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 224 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 2/249660 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.

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