Submissions for variant NM_000548.5(TSC2):c.*4C>T

gnomAD frequency: 0.00001  dbSNP: rs368282661

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000562957	SCV000675602	uncertain significance	Hereditary cancer-predisposing syndrome	2016-06-06	criteria provided, single submitter	clinical testing	The c.*4C>T variant is located in the 3' untranslated region (3’ UTR) of the TSC2 gene. This variant results from a C to T substitution 4 nucleotides after the last translated codon. This nucleotide position is poorly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Illumina Laboratory Services, Illumina	RCV001121427	SCV001280037	likely benign	Tuberous sclerosis syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001591342	SCV001823838	likely benign	not provided	2020-02-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001779015	SCV002014860	uncertain significance	not specified	2021-10-02	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001797753	SCV002040303	likely benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001591342	SCV004221403	uncertain significance	not provided	2023-09-07	criteria provided, single submitter	clinical testing	To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00015 (5/34008 chromosomes in Latino/Admixed American subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect TSC2 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant.
PreventionGenetics, part of Exact Sciences	RCV003935575	SCV004748004	likely benign	TSC2-related condition	2019-02-27	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).