Submissions for variant NM_000548.5(TSC2):c.3777C>T (p.Ser1259=)

gnomAD frequency: 0.00001  dbSNP: rs786202178

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164873	SCV000215558	likely benign	Hereditary cancer-predisposing syndrome	2014-11-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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	RCV000316816	SCV000395633	uncertain significance	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, 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001047638	SCV001211606	benign	Tuberous sclerosis 2	2023-12-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001668323	SCV001885645	likely benign	not provided	2020-12-17	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001047638	SCV002039782	likely benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000316816	SCV004822203	likely benign	Tuberous sclerosis syndrome	2023-10-06	criteria provided, single submitter	clinical testing