ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2561C>T (p.Pro854Leu)

gnomAD frequency: 0.00001  dbSNP: rs1180511535
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000552388 SCV000644355 likely benign Tuberous sclerosis 2 2024-01-14 criteria provided, single submitter clinical testing
GeneDx RCV001770442 SCV001992168 uncertain significance not provided 2019-04-29 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This substitution does not occur within known functional domains of the tuberin protein, where many pathogenic missense variants have been identified (Northrup et al., 2018; Au et al., 2007); This variant is associated with the following publications: (PMID: 30029678)
Genome-Nilou Lab RCV000552388 SCV002039664 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002456153 SCV002740216 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-23 criteria provided, single submitter clinical testing The p.P854L variant (also known as c.2561C>T), located in coding exon 22 of the TSC2 gene, results from a C to T substitution at nucleotide position 2561. The proline at codon 854 is replaced by leucine, an amino acid with similar properties. This alteration was identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS One, 2018 Apr;13:e0194098). 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.

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