ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4662G>A (p.Gln1554=) (rs137854880)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001224625 SCV001396837 pathogenic Tuberous sclerosis 2 2019-07-19 criteria provided, single submitter clinical testing This sequence change affects codon 1554 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 36 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 observed to be de novo in an individual affected with tuberous sclerosis (Invitae). ClinVar contains an entry for this variant (Variation ID: 49485). 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. For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC2) RCV000042745 SCV000066540 not provided Tuberous sclerosis syndrome no assertion provided curation

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