Submissions for variant NM_000548.5(TSC2):c.2031C>T (p.Pro677=)

gnomAD frequency: 0.00361  dbSNP: rs45517208

Total submissions: 23

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000175404	SCV000169120	benign	not specified	2012-12-13	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	RCV000163346	SCV000213880	likely benign	Hereditary cancer-predisposing syndrome	2014-10-14	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.
Eurofins Ntd Llc (ga)	RCV000175404	SCV000226880	likely benign	not specified	2015-01-12	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000175404	SCV000249206	benign	not specified	2021-10-19	criteria provided, single submitter	clinical testing
Invitae	RCV000203878	SCV000262258	benign	Tuberous sclerosis 2	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000175404	SCV000305164	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000042878	SCV000395598	likely benign	Tuberous sclerosis syndrome	2018-05-01	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	RCV000588605	SCV000697462	benign	not provided	2016-08-23	criteria provided, single submitter	clinical testing	Variant summary: The c.2031C>T (p.Pro677=) in TSC2 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.003 (156/47170 chrs tested), predominantly in individuals of European descent (0.006; 136/24126). This frequency exceeds the estimated maximum allele frequency for a pathogenic allele in this gene (0.0000068). The variant of interest has been cited as Benign/Likely Benign by multiple reputable databases/clinical laboratories. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000175404	SCV000711364	benign	not specified	2016-05-20	criteria provided, single submitter	clinical testing	p.Pro677Pro in exon 19 of TSC2: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.5% (136/24126) o f European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs45517208).
Athena Diagnostics Inc	RCV000175404	SCV000844563	benign	not specified	2017-05-30	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588605	SCV001473744	benign	not provided	2022-09-12	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000203878	SCV002039608	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000588605	SCV002497856	benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	TSC2: BP4, BP7, BS1, BS2
Sema4, Sema4	RCV000163346	SCV002531027	benign	Hereditary cancer-predisposing syndrome	2020-05-10	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000175404	SCV002774067	benign	not specified	2021-06-21	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000203878	SCV004360874	benign	Tuberous sclerosis 2	2022-08-17	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000042878	SCV000066674	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000175404	SCV001743015	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000588605	SCV001808927	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000175404	SCV001917609	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000175404	SCV001955600	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000175404	SCV001968599	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000588605	SCV002036444	likely benign	not provided		no assertion criteria provided	clinical testing