ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.130A>G (p.Ile44Val)

dbSNP: rs1555494697
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000574862 SCV000675709 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-07 criteria provided, single submitter clinical testing The p.I44V variant (also known as c.130A>G), located in coding exon 1 of the TSC2 gene, results from an A to G substitution at nucleotide position 130. The isoleucine at codon 44 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well 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.
Invitae RCV003626626 SCV004399813 uncertain significance Tuberous sclerosis 2 2023-04-13 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 44 of the TSC2 protein (p.Ile44Val). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 486649).

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