ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3487G>T (p.Ala1163Ser)

gnomAD frequency: 0.00001  dbSNP: rs560522093
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000685058 SCV000812530 benign Tuberous sclerosis 2 2024-01-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001020422 SCV001181900 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-26 criteria provided, single submitter clinical testing The p.A1163S variant (also known as c.3487G>T), located in coding exon 29 of the TSC2 gene, results from a G to T substitution at nucleotide position 3487. The alanine at codon 1163 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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.
Illumina Laboratory Services, Illumina RCV001117666 SCV001275880 benign Tuberous sclerosis syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Genome-Nilou Lab RCV000685058 SCV002039758 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001117666 SCV004822365 uncertain significance Tuberous sclerosis syndrome 2023-10-06 criteria provided, single submitter clinical testing This missense variant replaces alanine with serine at codon 1163 of the TSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 been identified in 1/250222 chromosomes 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.

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