ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.663+1G>A (rs118203419)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484162 SCV000568368 pathogenic not provided 2016-10-12 criteria provided, single submitter clinical testing This variant is denoted TSC1 c.663+1G>A or IVS7+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 7 of the TSC1 gene. TSC1 c.663+1G>A has not, to our knowledge, been published in the literature as a germline variant; however, it has been reported as a somatic variant in bladder cancer (Adachi 2003). This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. Based on the current evidence, we consider this variant to be pathogenic.
Invitae RCV000686448 SCV000813967 likely pathogenic Tuberous sclerosis 1 2018-04-24 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 of the TSC1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. 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: 49076). Donor and acceptor splice site variants 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Tuberous sclerosis database (TSC1) RCV000042329 SCV000066118 not provided Bladder cancer, somatic no assertion provided curation

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