ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3980A>G (p.Asp1327Gly)

dbSNP: rs1555513553
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567243 SCV000675739 uncertain significance Hereditary cancer-predisposing syndrome 2016-08-12 criteria provided, single submitter clinical testing The p.D1327G variant (also known as c.3980A>G), located in coding exon 32 of the TSC2 gene, results from an A to G substitution at nucleotide position 3980. The aspartic acid at codon 1327 is replaced by glycine, an amino acid with 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 6481 samples (12962 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.006% (greater than 20000 alleles tested) in our clinical cohort. This amino acid position is not 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 RCV001231583 SCV001404111 uncertain significance Tuberous sclerosis 2 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1327 of the TSC2 protein (p.Asp1327Gly). This variant is not present in population databases (gnomAD no frequency). 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: 486671). 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.
Genome-Nilou Lab RCV001231583 SCV002040800 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing

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