Submissions for variant NM_000548.5(TSC2):c.5117G>A (p.Arg1706His)

gnomAD frequency: 0.00006  dbSNP: rs45517392

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000233434	SCV000243611	likely benign	not provided	2021-06-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25186949, 27535533, 27170661, 32830346)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079298	SCV000285441	benign	Tuberous sclerosis 2	2024-01-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000576072	SCV000675547	likely benign	Hereditary cancer-predisposing syndrome	2021-07-23	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.
CeGaT Center for Human Genetics Tuebingen	RCV000233434	SCV001150722	uncertain significance	not provided	2016-05-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001079298	SCV002040252	likely benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000576072	SCV002534017	likely benign	Hereditary cancer-predisposing syndrome	2021-06-30	criteria provided, single submitter	curation
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000233434	SCV003799919	likely benign	not provided	2022-08-23	criteria provided, single submitter	clinical testing
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153329	SCV003843270	benign	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001079298	SCV004360937	uncertain significance	Tuberous sclerosis 2	2023-11-29	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with histidine at codon 1706 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with renal carcinoma in the literature (PMID: 32830346). This variant has been identified in 22/281760 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001079298	SCV005374384	likely benign	Tuberous sclerosis 2	2024-09-22	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000042716	SCV000066511	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000233434	SCV001980608	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004537167	SCV004754057	likely benign	TSC2-related disorder	2024-02-20	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).