Submissions for variant NM_000548.5(TSC2):c.4348C>G (p.Pro1450Ala)

gnomAD frequency: 0.00001  dbSNP: rs376381196

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000550016	SCV000644529	likely benign	Tuberous sclerosis 2	2024-12-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001569152	SCV001793161	likely benign	not provided	2019-06-17	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; 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)
Genome-Nilou Lab	RCV000550016	SCV002039456	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002330903	SCV002633082	uncertain significance	Hereditary cancer-predisposing syndrome	2024-02-06	criteria provided, single submitter	clinical testing	The p.P1450A variant (also known as c.4348C>G), located in coding exon 33 of the TSC2 gene, results from a C to G substitution at nucleotide position 4348. The proline at codon 1450 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly 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.