Submissions for variant NM_000368.5(TSC1):c.1460C>G (p.Ser487Cys)

gnomAD frequency: 0.00019  dbSNP: rs118203532

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000034602	SCV000243461	benign	not provided	2019-04-18	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21309039, 27153395, 16554133, 23514105, 22703879, 31054281)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001085737	SCV000284676	benign	Tuberous sclerosis 1	2024-01-28	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000189811	SCV000342691	likely benign	not specified	2016-06-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001085737	SCV000478231	likely benign	Tuberous sclerosis 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000319085	SCV000478232	likely benign	Isolated focal cortical dysplasia type II	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Ambry Genetics	RCV000568490	SCV000664629	likely benign	Hereditary cancer-predisposing syndrome	2018-08-08	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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV000761004	SCV000890919	uncertain significance	Primitive neuroectodermal tumor	2016-03-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034602	SCV001502115	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	TSC1: BS1
Genome-Nilou Lab	RCV001085737	SCV002040105	benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000189811	SCV002050786	likely benign	not specified	2021-12-06	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000568490	SCV002530908	likely benign	Hereditary cancer-predisposing syndrome	2020-10-27	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000034602	SCV004221381	benign	not provided	2016-06-09	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001085737	SCV004360825	benign	Tuberous sclerosis 1	2022-08-31	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034602	SCV000043515	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.
Tuberous sclerosis database (TSC1)	RCV000054845	SCV000065815	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
University of Washington Department of Laboratory Medicine, University of Washington	RCV001085737	SCV002568354	likely benign	Tuberous sclerosis 1	2019-10-29	no assertion criteria provided	clinical testing	This variant is present in approximately 1/280 individuals in an unaffected control population of East Asian ancestry (gnomAD). This variant has been reported in one individual with Tuberous Sclerosis (TSC1) (Choi et al., 2006). However, it was considered to be likely neutral by functional studies (Hoogeveen_Westerveld et al., 2011). Furthermore, this variant was identified as an incidental finding in one individual in a series of 566 individuals undergoing exome sequencing (Johnston et al., 2012). This variant is listed in ClinVar (Variation ID: 41690). Family studies were performed and showed that this variant was inherited from an unaffected parent who has no features of TSC1-related disorders. Additionally, the patient's clinical features do not match a TSC phenotype.