ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3240A>C (p.Leu1080Phe)

dbSNP: rs371514669
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000644134 SCV000765824 benign Tuberous sclerosis 2 2024-01-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV002449026 SCV002611785 likely benign Hereditary cancer-predisposing syndrome 2023-06-09 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
GeneDx RCV003128676 SCV003805893 likely benign not provided 2018-10-11 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000644134 SCV004171415 uncertain significance Tuberous sclerosis 2 2023-11-13 criteria provided, single submitter clinical testing The TSC2 c.3240A>C (p.Leu1080Phe) missense change has a maximum subpopulation frequency of 0.00089% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
All of Us Research Program, National Institutes of Health RCV004003999 SCV004817476 uncertain significance Tuberous sclerosis syndrome 2023-11-30 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 1080 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 hereditary cancer in the literature. This variant has been identified in 1/250106 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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