ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4460C>G (p.Ser1487Cys)

gnomAD frequency: 0.00001  dbSNP: rs766916450
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000691941 SCV000819740 uncertain significance Tuberous sclerosis 2 2023-09-03 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: 570942). 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 cysteine, which is neutral and slightly polar, at codon 1487 of the TSC2 protein (p.Ser1487Cys).
Ambry Genetics RCV002332432 SCV002635548 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-10 criteria provided, single submitter clinical testing The p.S1487C variant (also known as c.4460C>G), located in coding exon 33 of the TSC2 gene, results from a C to G substitution at nucleotide position 4460. The serine at codon 1487 is replaced by cysteine, an amino acid with dissimilar properties. This variant was detected in a cohort of 290 individuals with non-syndromic autism spectrum disorder (ASD) who had at least one sibling with ASD (Kelleher RJ et al. PLoS One, 2012 Apr;7:e35003). 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.
Fulgent Genetics, Fulgent Genetics RCV002485649 SCV002783392 uncertain significance Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 2022-02-21 criteria provided, single submitter clinical testing

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