ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4685T>C (p.Leu1562Pro)

dbSNP: rs45517362
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000713940 SCV000844587 likely pathogenic not provided 2021-05-20 criteria provided, single submitter clinical testing This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. Exerimental evidence suggests this variant results in an inactive form of the protein (www.lovd.nl/TSC2; PMID: 32502382). Computational tools predict that this variant is damaging.
Mendelics RCV000989438 SCV001139762 likely pathogenic Tuberous sclerosis 2 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV002336165 SCV002636283 likely pathogenic Hereditary cancer-predisposing syndrome 2017-11-14 criteria provided, single submitter clinical testing The p.L1562P variant (also known as c.4685T>C), located in coding exon 36 of the TSC2 gene, results from a T to C substitution at nucleotide position 4685. The leucine at codon 1562 is replaced by proline, an amino acid with similar properties. This alteration was detected in an individual with either a clinical diagnosis or high suspicion of tuberous sclerosis complex (TSC) and is localized in the GAP related domain of tuberin (Rosset C et al. PLoS ONE, 2017 Oct;12:e0185713). Based on internal structural analysis, this alteration is more destabilizing than known pathogenic variants (Daumke O et al. Nature, 2004 May;429(6988):197-201). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Tuberous sclerosis database (TSC2) RCV000043318 SCV000067124 not provided Tuberous sclerosis syndrome no assertion provided curation

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