ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.54G>C (p.Met18Ile) (rs940292214)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756827 SCV000884751 uncertain significance not provided 2017-12-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV000571184 SCV000675383 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000457262 SCV000552300 uncertain significance Tuberous sclerosis 1 2017-12-20 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 18 of the TSC1 protein (p.Met18Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TSC1-related disease. ClinVar contains an entry for this variant (Variation ID: 411236). 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 and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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