ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2639+1G>A

dbSNP: rs45517252
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000190003 SCV000243675 pathogenic not provided 2013-12-06 criteria provided, single submitter clinical testing c.2639+1 G>A: IVS23+1 G>A in intron 23 of the TSC2 gene (NM_000548.3)The c.2639+1 G>A splice site mutation in the TSC2 gene destroys the canonical splice donor site in intron 23. A different nucleotide substitution at this same position (c.2639+1 G>C) has been previously published in association with tuberous sclerosis (Dabora et al., 2001). The c.2639+1 G>A mutation is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. This mutation has not been previously reported to our knowledge. The variant is found in INFANT-EPI panel(s).
CeGaT Center for Human Genetics Tuebingen RCV000190003 SCV001500045 pathogenic not provided 2020-11-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001797674 SCV002040957 pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Invitae RCV001797674 SCV002125318 pathogenic Tuberous sclerosis 2 2020-12-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. This sequence change affects a donor splice site in intron 23 of the TSC2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). This variant has been observed in individual(s) with clinical features of tuberous sclerosis complex (PMID: 11112665, 32340510, 29655203, 24075384, 29476190). ClinVar contains an entry for this variant (Variation ID: 207733). This variant is not present in population databases (ExAC no frequency).
Athena Diagnostics Inc RCV000190003 SCV004229362 pathogenic not provided 2023-08-21 criteria provided, single submitter clinical testing This variant is expected to severely impact normal RNA splicing, and consequently, protein structure and/or function. This variant has been identified in at least one individual with clinical features associated with this gene. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).

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