ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.1315C>G (p.Leu439Val)

gnomAD frequency: 0.00001  dbSNP: rs199800297
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000560409 SCV000641502 benign Tuberous sclerosis 1 2023-10-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000573643 SCV000675352 benign Hereditary cancer-predisposing syndrome 2023-10-31 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.
GeneDx RCV001574705 SCV001801571 likely benign not provided 2020-11-20 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000560409 SCV002040112 likely benign Tuberous sclerosis 1 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000573643 SCV002530899 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-24 criteria provided, single submitter curation
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000560409 SCV002584724 uncertain significance Tuberous sclerosis 1 2022-07-11 criteria provided, single submitter clinical testing The TSC1 c.1315C>G (p.Leu439Val) missense change has a maximum subpopulation frequency of 0.0023% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with tuberous sclerosis complex. 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 RCV003999188 SCV004833416 uncertain significance Tuberous sclerosis syndrome 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces leucine with valine at codon 439 of the TSC1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC1-related disorders in the literature. This variant has been identified in 3/282750 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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