rs749487441
- Uncertain significance
Your Genotype
Sign InDescription
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1753 of the TSC2 protein (p.Arg1753Gln). This variant is present in population databases (rs749487441, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 233437). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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 p.R1753Q variant (also known as c.5258G>A), located in coding exon 40 of the TSC2 gene, results from a G to A substitution at nucleotide position 5258. The arginine at codon 1753 is replaced by glutamine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6492 samples (12984 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 20000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Reference Allele
G
Alternative Allele
A
C
T
Chromosome
16
Location
2088324
Variant Type
SNP
ClinVar
Name
NM_000548.5(TSC2):c.5258G>A (p.Arg1753Gln)
Allele
A
Clinical Significance
Uncertain significance