Submissions for variant NM_000368.5(TSC1):c.2865C>T (p.Thr955=)

gnomAD frequency: 0.00193  dbSNP: rs45468995

Total submissions: 23

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000152157	SCV000169095	benign	not specified	2013-10-08	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152157	SCV000200857	likely benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	Thr955Thr in exon 22 of TSC1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 0.2% (20/8600) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs45468995).
Ambry Genetics	RCV000163343	SCV000213877	likely benign	Hereditary cancer-predisposing syndrome	2014-11-04	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.
Eurofins Ntd Llc (ga)	RCV000152157	SCV000227886	likely benign	not specified	2014-07-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000205209	SCV000262139	benign	Tuberous sclerosis 1	2025-02-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000152157	SCV000303867	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000205209	SCV000478187	benign	Tuberous sclerosis 1	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000274884	SCV000478188	benign	Isolated focal cortical dysplasia type II	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Athena Diagnostics	RCV000205209	SCV000677529	benign	Tuberous sclerosis 1	2017-05-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001725957	SCV001474484	benign	not provided	2022-04-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001725957	SCV001962584	likely benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	TSC1: BP4, BP7, BS1
Genome-Nilou Lab	RCV000205209	SCV002040355	benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163343	SCV002528903	benign	Hereditary cancer-predisposing syndrome	2020-07-31	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000152157	SCV002774054	benign	not specified	2021-05-14	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002496670	SCV002805453	likely benign	Lymphangiomyomatosis; Tuberous sclerosis 1; Isolated focal cortical dysplasia type II	2021-07-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000152157	SCV003800740	benign	not specified	2023-01-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000205209	SCV004360802	likely benign	Tuberous sclerosis 1	2019-03-29	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000042259	SCV004840453	likely benign	Tuberous sclerosis syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC1)	RCV000042259	SCV000066046	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000152157	SCV001808514	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000152157	SCV001921850	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000152157	SCV001928743	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000152157	SCV001968223	benign	not specified		no assertion criteria provided	clinical testing