ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5299C>G (p.Leu1767Val)

gnomAD frequency: 0.00001  dbSNP: rs1051758
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000547303 SCV000644629 benign Tuberous sclerosis 2 2024-01-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV000570898 SCV000675654 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-13 criteria provided, single submitter clinical testing The p.L1767V variant (also known as c.5299C>G), located in coding exon 41 of the TSC2 gene, results from a C to G substitution at nucleotide position 5299. The leucine at codon 1767 is replaced by valine, an amino acid with highly similar properties. 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.
Genome-Nilou Lab RCV000547303 SCV002040277 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003403303 SCV004122000 uncertain significance not specified 2023-10-23 criteria provided, single submitter clinical testing Variant summary: TSC2 c.5299C>G (p.Leu1767Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 250266 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5299C>G in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as uncertain significance (n=1), benign (n=1), or likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.

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