ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5254C>T (p.Gln1752Ter)

dbSNP: rs45517414
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000271618 SCV000329792 likely pathogenic not provided 2021-07-15 criteria provided, single submitter clinical testing Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 56 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 17304050, 27535533)
Athena Diagnostics RCV000271618 SCV000615925 pathogenic not provided 2016-12-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV002313736 SCV000847491 pathogenic Hereditary cancer-predisposing syndrome 2016-08-09 criteria provided, single submitter clinical testing The p.Q1752* pathogenic mutation (also known as c.5254C>T), located in coding exon 40 of the TSC2 gene, results from a C to T substitution at nucleotide position 5254. This changes the amino acid from a glutamine to a stop codon within coding exon 40. This variant has been reported in an individual with a clinical diagnosis of tuberous sclerosis complex (Au KS et al. Genet. Med., 2007 Feb;9:88-100). In addition to the clinical data presented in the literature, this alteration is expected to escape nonsense-mediated mRNA decay and result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Genome-Nilou Lab RCV001797602 SCV002041031 likely pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001797602 SCV003441718 uncertain significance Tuberous sclerosis 2 2023-11-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1752*) in the TSC2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 56 amino acid(s) of the TSC2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 49367). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Tuberous sclerosis database (TSC2) RCV000042627 SCV000066421 not provided Tuberous sclerosis syndrome no assertion provided curation

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