ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4570-1G>A

gnomAD frequency: 0.00001  dbSNP: rs777985056
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000824388 SCV000965284 likely benign Tuberous sclerosis 2 2023-12-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV001022719 SCV001184487 uncertain significance Hereditary cancer-predisposing syndrome 2021-03-15 criteria provided, single submitter clinical testing The c.4570-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 35 of the TSC2 gene. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, this alteration is predicted to lead to an in frame loss of coding exon 35 and no known functional domains or pathogenic mutations are located in this exon. In addition, this alteration has been observed in a few families who do not have a personal or family history that is consistent with or suggestive of TSC2-associated disease (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV000824388 SCV001434941 likely pathogenic Tuberous sclerosis 2 2018-10-12 criteria provided, single submitter clinical testing This c.4570-1G>A variant in a canonical splice site acceptor site is predicted to result in a frameshift mutation resulting in a product , if any, without the GTPAse activating domain. The variant affects major biological transcripts and is consistent with loss of function disease mechanism of TSC2.The variant is absent in public databases. Therefore, this c.4570-1G>A variant in the TSC2 gene is classified as likely pathogenic.
Genome-Nilou Lab RCV000824388 SCV002040208 likely pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
GeneDx RCV002260671 SCV002540428 uncertain significance not provided 2023-09-11 criteria provided, single submitter clinical testing Canonical splice site variant with an unclear effect on protein function, although loss of an in-frame exon is predicted; Deletions involving coding exons of this gene are a known mechanism of disease (HGMD); This variant has not been reported in the literature in individuals with tuberous sclerosis complex (TSC) to our knowledge; Also known as IVS34-1 G>A; This variant is associated with the following publications: (PMID: 17304050, 10205261, 18466115, 16199547, 31447099)
Baylor Genetics RCV003461290 SCV004205111 uncertain significance Isolated focal cortical dysplasia type II 2023-01-01 criteria provided, single submitter clinical testing

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