ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.566G>C (p.Cys189Ser)

dbSNP: rs764218079
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001024388 SCV001186396 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-14 criteria provided, single submitter clinical testing The p.C189S variant (also known as c.566G>C), located in coding exon 5 of the TSC2 gene, results from a G to C substitution at nucleotide position 566. The cysteine at codon 189 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001315789 SCV001506381 uncertain significance Tuberous sclerosis 2 2020-02-04 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TSC2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with serine at codon 189 of the TSC2 protein (p.Cys189Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine.
Genome-Nilou Lab RCV001315789 SCV002040554 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004004649 SCV004837608 uncertain significance Tuberous sclerosis syndrome 2023-10-06 criteria provided, single submitter clinical testing This missense variant replaces cysteine with serine at codon 189 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 TSC2-related disorders 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.

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