Submissions for variant NM_000548.5(TSC2):c.4448G>C (p.Arg1483Thr) (rs370114027)

Minimum review status:		Collection method:
Minimum conflict level:
		ClinVar version:

Total submissions: 5

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000475203	SCV000544586	uncertain significance	Tuberous sclerosis 2	2018-01-23	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with threonine at codon 1483 of the TSC2 protein (p.Arg1483Thr). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and threonine. This variant is present in population databases (rs370114027, ExAC 0.006%). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 65332). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV000566285	SCV000675502	uncertain significance	Hereditary cancer-predisposing syndrome	2016-03-26	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx	RCV000831461	SCV000973210	likely benign	not provided	2018-06-20	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.
Tuberous sclerosis database (TSC2)	RCV000055556	SCV000083780	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Istituto Neurologico Mediterraneo,Istituto di Ricovero e Cura a Carattere Scientifico	RCV000475203	SCV000994608	benign	Tuberous sclerosis 2	2019-09-27	no assertion criteria provided	clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.