ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.1231C>A (p.Leu411Ile)

gnomAD frequency: 0.00003  dbSNP: rs397514840
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000474632 SCV000552325 benign Tuberous sclerosis 1 2023-11-30 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000761088 SCV000891003 uncertain significance Craniopharyngioma 2016-11-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000474632 SCV002040118 likely benign Tuberous sclerosis 1 2021-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002362687 SCV002664196 likely benign Hereditary cancer-predisposing syndrome 2020-12-29 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.
All of Us Research Program, National Institutes of Health RCV000054977 SCV004840467 uncertain significance Tuberous sclerosis syndrome 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces leucine with isoleucine at codon 411 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). An experimental functional study demonstrated a similar impact on mammalian target of rapamycin complex 1 (TORC1) inhibition as wild-type TSC1 (PMID: 22161988). This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251184 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.
Tuberous sclerosis database (TSC1) RCV000054977 SCV000083195 not provided Tuberous sclerosis syndrome no assertion provided curation

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