Submissions for variant NM_000548.5(TSC2):c.1004C>T (p.Ser335Phe)

gnomAD frequency: 0.00001  dbSNP: rs45517144

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000694942	SCV000823412	benign	Tuberous sclerosis 2	2023-12-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001009666	SCV001169763	uncertain significance	Hereditary cancer-predisposing syndrome	2023-08-21	criteria provided, single submitter	clinical testing	The p.S335F variant (also known as c.1004C>T), located in coding exon 10 of the TSC2 gene, results from a C to T substitution at nucleotide position 1004. The serine at codon 335 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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	RCV000694942	SCV001435081	uncertain significance	Tuberous sclerosis 2		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000694942	SCV002040584	uncertain significance	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001009666	SCV002532735	uncertain significance	Hereditary cancer-predisposing syndrome	2022-02-11	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000694942	SCV005404881	likely benign	Tuberous sclerosis 2	2024-08-07	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.