ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1004C>G (p.Ser335Cys)

dbSNP: rs45517144
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000202762 SCV000257717 uncertain significance Tuberous sclerosis 2 2015-07-10 criteria provided, single submitter clinical testing
Baylor Genetics RCV003466895 SCV004206837 uncertain significance Isolated focal cortical dysplasia type II 2023-09-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000202762 SCV004284418 uncertain significance Tuberous sclerosis 2 2024-11-18 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 335 of the TSC2 protein (p.Ser335Cys). 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: 49653). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Ambry Genetics RCV004018922 SCV005036135 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-20 criteria provided, single submitter clinical testing The p.S335C variant (also known as c.1004C>G), located in coding exon 10 of the TSC2 gene, results from a C to G substitution at nucleotide position 1004. The serine at codon 335 is replaced by cysteine, 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. Based on the available evidence, the clinical significance of this alteration remains unclear.
Tuberous sclerosis database (TSC2) RCV000042915 SCV000066711 not provided Tuberous sclerosis syndrome no assertion provided curation

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