ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.1772C>A (p.Pro591Gln) (rs768985094)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000535112 SCV000641520 uncertain significance Tuberous sclerosis 1 2017-10-19 criteria provided, single submitter clinical testing This sequence change replaces proline with glutamine at codon 591 of the TSC1 protein (p.Pro591Gln). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and glutamine. This variant is present in population databases (rs768985094, ExAC 0.001%) but has not been reported in the literature in individuals with a TSC1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000567125 SCV000675391 likely benign Hereditary cancer-predisposing syndrome 2016-07-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting benign classification,In silico models in agreement (benign)

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