ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4662G>T (p.Gln1554His) (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 RCV001232925 SCV001405498 pathogenic Tuberous sclerosis 2 2019-08-08 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 1554 of the TSC2 protein (p.Gln1554His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. 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 (PMID: 16114042). ClinVar contains an entry for this variant (Variation ID: 49486). This variant has been reported to affect TSC2 protein function (PMID: 16114042, 22903760). 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) RCV000042746 SCV000066541 not provided Tuberous sclerosis syndrome no assertion provided curation

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