ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1599G>A (p.Lys533=) (rs1555502589)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001056287 SCV001220723 uncertain significance Tuberous sclerosis 2 2019-04-24 criteria provided, single submitter clinical testing This sequence change affects codon 533 of the TSC2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the TSC2 protein. This variant also falls at the last nucleotide of exon 15 of the TSC2 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 49686). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. A different variant affecting this nucleotide (c.1599G>C) has been determined to be pathogenic (PMID:27859028). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. 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) RCV000042949 SCV000066746 not provided Tuberous sclerosis syndrome no assertion provided curation

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