Submissions for variant NM_000548.5(TSC2):c.4397C>T (p.Ser1466Leu)

gnomAD frequency: 0.00003  dbSNP: rs45517341

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000226937	SCV000285402	likely benign	Tuberous sclerosis 2	2024-01-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000422566	SCV000517302	likely benign	not specified	2018-02-01	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV002315686	SCV000847935	uncertain significance	Hereditary cancer-predisposing syndrome	2021-01-11	criteria provided, single submitter	clinical testing	The p.S1466L variant (also known as c.4397C>T), located in coding exon 33 of the TSC2 gene, results from a C to T substitution at nucleotide position 4397. The serine at codon 1466 is replaced by leucine, an amino acid with dissimilar properties. This variant was identified in conjunction with a pathogenic TSC2 mutation in a familial TSC kindred (Rosset C et al. PLoS One, 2017 Oct;12:e0185713). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV000226937	SCV002040188	likely benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003390985	SCV004129861	uncertain significance	not provided	2023-06-01	criteria provided, single submitter	clinical testing