Submissions for variant NM_000548.5(TSC2):c.1133C>T (p.Pro378Leu)

gnomAD frequency: 0.00003  dbSNP: rs45517154

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001084867	SCV000285226	benign	Tuberous sclerosis 2	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000572792	SCV000675561	likely benign	Hereditary cancer-predisposing syndrome	2018-08-14	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.
GeneDx	RCV000842561	SCV000984585	likely benign	not provided	2021-05-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23514105, 19139070, 10205261)
Illumina Laboratory Services, Illumina	RCV000043432	SCV001277277	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genome-Nilou Lab	RCV001084867	SCV002041132	likely benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000572792	SCV002532752	likely benign	Hereditary cancer-predisposing syndrome	2021-06-24	criteria provided, single submitter	curation
Tuberous sclerosis database (TSC2)	RCV000043432	SCV000067239	not provided	Tuberous sclerosis syndrome		no assertion provided	curation