Submissions for variant NM_000368.5(TSC1):c.3103G>A (p.Gly1035Ser)

gnomAD frequency: 0.00139  dbSNP: rs118203742

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000122196	SCV000169096	benign	not specified	2013-10-01	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.
Ambry Genetics	RCV000130763	SCV000185655	benign	Hereditary cancer-predisposing syndrome	2014-12-03	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Genetic Services Laboratory, University of Chicago	RCV000122196	SCV000249203	benign	not specified	2021-08-19	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080484	SCV000261866	benign	Tuberous sclerosis 1	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000122196	SCV000303868	likely benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000122196	SCV000333780	likely benign	not specified	2015-08-04	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000297382	SCV000478183	likely benign	Isolated focal cortical dysplasia type II	2018-09-25	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001080484	SCV000478184	likely benign	Tuberous sclerosis 1	2018-09-25	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000034609	SCV000696608	benign	not provided	2016-08-31	criteria provided, single submitter	clinical testing	Variant Summary: The c.3103G>A (p.Gly1035Ser) in TSC1 gene is a missense change that involves a non-conserved nucleotide and 3/4 in silico programs predicting a "benign" outcome. The variant of interest was observed in controls with an allele frequency of 0.0014 (170/119052chrs tested) which exceeds the predicted maximum expected allele frequency for a pathogenic variant in this gene (0.0025). The variant of interest has been reported in multiple affected individuals in cis with a pathogenic variant (Nellist, 2009, TSC1 db).In the functional studies the G1035S had similar activities as wt (Nellist, 2009). In addition, multiple reputable databases/clinical laboratories and publications cite the variant with a classification of "Neutral/likely benign." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as a Benign.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000034609	SCV002009242	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001080484	SCV002040015	benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000130763	SCV002531419	benign	Hereditary cancer-predisposing syndrome	2020-09-24	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000122196	SCV002774055	benign	not specified	2021-08-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034609	SCV003917725	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	TSC1: BP4, BS1
Color Diagnostics, LLC DBA Color Health	RCV001080484	SCV004360799	benign	Tuberous sclerosis 1	2022-10-09	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034609	SCV004563124	benign	not provided	2023-10-26	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034609	SCV000043507	probably not pathogenic	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Likely benign.
Tuberous sclerosis database (TSC1)	RCV000054850	SCV000066052	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
ITMI	RCV000122196	SCV000086415	not provided	not specified	2013-09-19	no assertion provided	reference population
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000122196	SCV001966233	benign	not specified		no assertion criteria provided	clinical testing