ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.121C>T (p.Leu41Phe)

gnomAD frequency: 0.00001  dbSNP: rs118203334
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000525235 SCV000641488 likely benign Tuberous sclerosis 1 2024-01-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV001010403 SCV001170601 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-15 criteria provided, single submitter clinical testing The p.L41F variant (also known as c.121C>T), located in coding exon 2 of the TSC1 gene, results from a C to T substitution at nucleotide position 121. The leucine at codon 41 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000525235 SCV002040182 likely benign Tuberous sclerosis 1 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001010403 SCV002530886 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-06 criteria provided, single submitter curation
PreventionGenetics, part of Exact Sciences RCV003424114 SCV004108466 uncertain significance TSC1-related disorder 2023-08-28 criteria provided, single submitter clinical testing The TSC1 c.121C>T variant is predicted to result in the amino acid substitution p.Leu41Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-135802677-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
All of Us Research Program, National Institutes of Health RCV003999185 SCV004840567 uncertain significance Tuberous sclerosis syndrome 2024-01-11 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 41 of the TSC1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 TSC1-related disorders in the literature. This variant has been identified in 1/251120 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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