Submissions for variant NM_000548.5(TSC2):c.5135C>T (p.Ala1712Val)

gnomAD frequency: 0.00001  dbSNP: rs45517394

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000706814	SCV000835885	benign	Tuberous sclerosis 2	2023-09-15	criteria provided, single submitter	clinical testing
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	RCV000706814	SCV001435085	uncertain significance	Tuberous sclerosis 2		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000706814	SCV002040253	likely benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002343574	SCV002646611	uncertain significance	Hereditary cancer-predisposing syndrome	2024-03-08	criteria provided, single submitter	clinical testing	The p.A1712V variant (also known as c.5135C>T), located in coding exon 39 of the TSC2 gene, results from a C to T substitution at nucleotide position 5135. The alanine at codon 1712 is replaced by valine, an amino acid with similar properties. In one study, this alteration was observed in an individual with a personal history that is consistent with TSC2-related disease (Ludwig K et al. Front Immunol, 2020 Aug;11:1515). This amino acid position is well conserved in available vertebrate species; however, valine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.