ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2023_2024delinsTT (p.Ala675Leu)

dbSNP: rs1555506090
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000554874 SCV000644312 uncertain significance Tuberous sclerosis 2 2024-01-12 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 675 of the TSC2 protein (p.Ala675Leu). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the 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: 467917). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV000563982 SCV000675787 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-20 criteria provided, single submitter clinical testing The c.2023_2024delGCinsTT variant (also known as p.A675L), located in coding exon 18 of the TSC2 gene, results from a deletion of GC and insertion of TT at nucleotide positions 2023 to 2024. This results in the substitution of the alanine residue for a leucine residue at codon 675, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000554874 SCV002040668 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing

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