ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.1997+1G>A

dbSNP: rs118203610
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189849 SCV000243502 pathogenic not provided 2017-01-30 criteria provided, single submitter clinical testing The c.1997+1 G>A splice site variant in the TSC1 gene has been reported multiple times previously in association with tuberous sclerosis complex (TSC) (Au et al., 2007; TSC1 LOVD). This pathogenic variant destroys the canonical donor site in intron 15. It 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002514165 SCV003441395 pathogenic Tuberous sclerosis 1 2024-05-28 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 15 of the TSC1 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 TSC1 are known to be pathogenic (PMID: 10227394, 17304050). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with tuberous sclerosis complex (PMID: 20633017, 21520333). ClinVar contains an entry for this variant (Variation ID: 48863). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV002514165 SCV005083677 likely pathogenic Tuberous sclerosis 1 2024-06-03 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.
Tuberous sclerosis database (TSC1) RCV000042114 SCV000065899 not provided Tuberous sclerosis syndrome no assertion provided curation

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