ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.2341C>T (p.Gln781Ter)

dbSNP: rs118203680
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000473593 SCV000552248 pathogenic Tuberous sclerosis 1 2023-02-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln781*) in the TSC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC1 are known to be pathogenic (PMID: 10227394, 17304050). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with tuberous sclerosis complex (PMID: 29500070, 32313033). ClinVar contains an entry for this variant (Variation ID: 48941). For these reasons, this variant has been classified as Pathogenic.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002054843 SCV002496012 pathogenic Lymphangiomyomatosis; Tuberous sclerosis 1; Isolated focal cortical dysplasia type II 2021-03-30 criteria provided, single submitter clinical testing TSC1 NM_000368.4 exon 18 p.Gln781* (c.2341C>T): This variant has been reported in several individuals with tuberous sclerosis in the Leiden Open-source Variation Database (LOVD) (https://databases.lovd.nl/shared/variants/TSC1). This variant is not present in large control databases but is present in ClinVar (Variation ID:48941). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is predicted to cause a stopgain at this codon, resulting in protein truncation or loss of allelic expression through nonsense-mediated mRNA decay. Loss of function variants are a known mechanism of disease for this gene (Rosset 2017 PMID:28222202). In summary, this variant is classified as pathogenic based on the data above.
Ambry Genetics RCV002426584 SCV002731859 pathogenic Hereditary cancer-predisposing syndrome 2018-01-23 criteria provided, single submitter clinical testing The p.Q781* pathogenic mutation (also known as c.2341C>T), located in coding exon 16 of the TSC1 gene, results from a C to T substitution at nucleotide position 2341. This changes the amino acid from a glutamine to a stop codon within coding exon 16. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Tuberous sclerosis database (TSC1) RCV000042192 SCV000065978 not provided Tuberous sclerosis syndrome no assertion provided curation

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