ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.772G>A (p.Glu258Lys) (rs118203450)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189841 SCV000243494 uncertain significance not provided 2018-05-10 criteria provided, single submitter clinical testing This variant is denoted TSC1 c.772G>A at the cDNA level, p.Glu258Lys (E258K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAG>AAG). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. TSC1 Glu258Lys was observed at an allele frequency of 0.01% in individuals of African ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether TSC1 Glu258Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000641992 SCV000478255 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). 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 Clinical Services Laboratory,Illumina RCV000376049 SCV000478256 likely benign 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). 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.
Invitae RCV000641992 SCV000763644 uncertain significance Tuberous sclerosis 1 2019-11-01 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 258 of the TSC1 protein (p.Glu258Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs118203450, ExAC 0.01%). This variant has not been reported in the literature in individuals with TSC1-related disease. ClinVar contains an entry for this variant (Variation ID: 207627). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.