ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.1916G>A (p.Gly639Asp) (rs372583166)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538760 SCV000641532 uncertain significance Tuberous sclerosis 1 2018-09-22 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 639 of the TSC1 protein (p.Gly639Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs372583166, ExAC 0.009%) 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect 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 RCV000563536 SCV000675459 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-24 criteria provided, single submitter clinical testing Insufficient evidence;In silico models in agreement (benign)

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