Submissions for variant NM_000548.5(TSC2):c.270G>A (p.Gln90=)

gnomAD frequency: 0.00002  dbSNP: rs779310889

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000538146	SCV000644362	benign	Tuberous sclerosis 2	2023-10-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001016247	SCV001177181	likely benign	Hereditary cancer-predisposing syndrome	2018-12-28	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina	RCV001120818	SCV001279328	likely benign	Tuberous sclerosis syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001545071	SCV001764330	likely benign	not provided	2019-09-26	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000538146	SCV002041199	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003900185	SCV004711461	likely benign	TSC2-related condition	2023-12-04	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).