ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3022G>A (p.Val1008Met) (rs397514985)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000644223 SCV000765914 uncertain significance Tuberous sclerosis 2 2018-03-02 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 1008 of the TSC2 protein (p.Val1008Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs397514985, ExAC 0.02%). This variant has been observed in an individual with tuberous sclerosis complex in the Leiden Open-source Variation Database (PMID: 21520333). However, in that individual a pathogenic allele was also identified in TSC2, which suggests that this c.3022G>A variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 64980). 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 methionine 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 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.
Tuberous sclerosis database (TSC2) RCV000055183 SCV000083401 not provided Tuberous sclerosis syndrome no assertion provided curation

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