Submissions for variant NM_000548.5(TSC2):c.1292C>T (p.Ala431Val)

gnomAD frequency: 0.00030  dbSNP: rs202187148

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000710274	SCV000243643	benign	not provided	2020-08-26	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32555378, 23514105, 25862857, 22558107)
Invitae	RCV001079695	SCV000285234	benign	Tuberous sclerosis 2	2024-01-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003891755	SCV000305142	likely benign	TSC2-related condition	2019-07-15	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).
Illumina Laboratory Services, Illumina	RCV000284623	SCV000395575	likely benign	Tuberous sclerosis syndrome	2018-01-12	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.
Athena Diagnostics Inc	RCV000710274	SCV000615881	benign	not provided	2018-04-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000563838	SCV000675499	likely benign	Hereditary cancer-predisposing syndrome	2018-06-04	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.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001199344	SCV001370430	likely benign	Lymphangiomyomatosis	2019-06-21	criteria provided, single submitter	clinical testing	This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: PP3,BP6,BS1.
CeGaT Center for Human Genetics Tuebingen	RCV000710274	SCV001747136	likely benign	not provided	2023-08-01	criteria provided, single submitter	clinical testing	TSC2: BS1
Genome-Nilou Lab	RCV001079695	SCV002041315	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000563838	SCV002532764	benign	Hereditary cancer-predisposing syndrome	2020-12-16	criteria provided, single submitter	curation