Submissions for variant NM_000548.5(TSC2):c.2153G>A (p.Arg718His)

dbSNP: rs45517215

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166299	SCV000217083	uncertain significance	Hereditary cancer-predisposing syndrome	2023-07-13	criteria provided, single submitter	clinical testing	The p.R718H variant (also known as c.2153G>A), located in coding exon 19 of the TSC2 gene, results from a G to A substitution at nucleotide position 2153. The arginine at codon 718 is replaced by histidine, an amino acid with highly similar properties. This alteration was identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS One, 2018 Apr;13:e0194098). This amino acid position is not 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	RCV000469825	SCV000544419	likely benign	Tuberous sclerosis 2	2024-12-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001589035	SCV001825876	likely benign	not provided	2020-11-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000469825	SCV002039624	likely benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing