ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.820T>G (p.Tyr274Asp)

dbSNP: rs367642937
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000465565 SCV000544324 uncertain significance Tuberous sclerosis 2 2023-10-30 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 274 of the TSC2 protein (p.Tyr274Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 405958). 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 TSC2 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 RCV002429485 SCV002678278 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-20 criteria provided, single submitter clinical testing The p.Y274D variant (also known as c.820T>G), located in coding exon 8 of the TSC2 gene, results from a T to G substitution at nucleotide position 820. The tyrosine at codon 274 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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