Submissions for variant NM_000548.5(TSC2):c.4256A>G (p.Gln1419Arg)

gnomAD frequency: 0.00001  dbSNP: rs562443546

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000568648	SCV000675665	uncertain significance	Hereditary cancer-predisposing syndrome	2021-01-05	criteria provided, single submitter	clinical testing	The p.Q1419R variant (also known as c.4256A>G), located in coding exon 33 of the TSC2 gene, results from an A to G substitution at nucleotide position 4256. The glutamine at codon 1419 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000644236	SCV000765927	benign	Tuberous sclerosis 2	2023-12-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001558891	SCV001780926	uncertain significance	not provided	2019-08-22	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This substitution does not occur within known functional domains of the tuberin protein, where many pathogenic missense variants have been identified (Northrup et al., 2018; Au et al., 2007); Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab	RCV000644236	SCV002040813	uncertain significance	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002476253	SCV002783890	uncertain significance	Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2	2022-03-04	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000644236	SCV005407419	likely benign	Tuberous sclerosis 2	2024-08-20	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.