ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.1729G>A (p.Glu577Lys)

dbSNP: rs118203570
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001071045 SCV001236327 uncertain significance Tuberous sclerosis 1 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 577 of the TSC1 protein (p.Glu577Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 863958). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC1 protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV002411618 SCV002715645 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-04 criteria provided, single submitter clinical testing The p.E577K variant (also known as c.1729G>A), located in coding exon 13 of the TSC1 gene, results from a G to A substitution at nucleotide position 1729. The glutamic acid at codon 577 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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.

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