Submissions for variant NM_000548.5(TSC2):c.1599+5G>A

dbSNP: rs397515100

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000816898	SCV000957427	pathogenic	Tuberous sclerosis 2	2023-07-10	criteria provided, single submitter	clinical testing	This sequence change falls in intron 15 of the TSC2 gene. It does not directly change the encoded amino acid sequence of the TSC2 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with tuberous sclerosis (PMID: 21520333). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 65133). Variants that disrupt 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 create or strengthen a splice site. This variant disrupts the c.1599+5G nucleotide in the TSC2 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (www.lovd.nl/TSC2). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV001012363	SCV001172801	uncertain significance	Hereditary cancer-predisposing syndrome	2018-09-07	criteria provided, single submitter	clinical testing	The c.1599+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 14 in the TSC2 gene. This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV000816898	SCV002039557	uncertain significance	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000055346	SCV000083566	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Tuberous sclerosis database (TSC2)	RCV000055346	SCV000083764	not provided	Tuberous sclerosis syndrome		no assertion provided	curation