ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3650G>A (p.Ser1217Asn)

dbSNP: rs2151481330
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001955694 SCV002220083 uncertain significance Tuberous sclerosis 2 2022-07-19 criteria provided, single submitter clinical testing 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: 1443610). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1217 of the TSC2 protein (p.Ser1217Asn).
All of Us Research Program, National Institutes of Health RCV004010964 SCV004822336 uncertain significance Tuberous sclerosis syndrome 2023-04-03 criteria provided, single submitter clinical testing This missense variant replaces serine with asparagine at codon 1217 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with tuberous sclerosis complex in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004681348 SCV005174596 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-14 criteria provided, single submitter clinical testing The p.S1217N variant (also known as c.3650G>A), located in coding exon 30 of the TSC2 gene, results from a G to A substitution at nucleotide position 3650. The serine at codon 1217 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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