Submissions for variant NM_000548.5(TSC2):c.2437G>A (p.Val813Met)

gnomAD frequency: 0.00002  dbSNP: rs375030314

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000535705	SCV000644345	likely benign	Tuberous sclerosis 2	2024-01-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001015534	SCV001176379	uncertain significance	Hereditary cancer-predisposing syndrome	2022-01-25	criteria provided, single submitter	clinical testing	The p.V813M variant (also known as c.2437G>A), located in coding exon 21 of the TSC2 gene, results from a G to A substitution at nucleotide position 2437. The valine at codon 813 is replaced by methionine, 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 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	RCV000535705	SCV002039653	likely benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153712	SCV003843646	likely pathogenic	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing