ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4006-8C>T (rs45517325)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000177764 SCV000169145 benign not specified 2013-08-01 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000177764 SCV000229692 benign not specified 2014-11-14 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000177764 SCV000305213 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000042540 SCV000395641 likely benign Tuberous sclerosis syndrome 2018-10-02 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae RCV000472266 SCV000556679 benign Tuberous sclerosis 2 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000177764 SCV001338284 benign not specified 2020-02-07 criteria provided, single submitter clinical testing Variant summary: TSC2 c.4006-8C>T alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0025 in 189510 control chromosomes in the gnomAD database, including 4 homozygotes. The observed variant frequency is approximately 36.61 fold of the estimated maximal expected allele frequency for a pathogenic variant in TSC2 causing Tuberous Sclerosis Complex phenotype (6.9e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.4006-8C>T in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Tuberous sclerosis database (TSC2) RCV000042540 SCV000066333 not provided Tuberous sclerosis syndrome no assertion provided curation

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