ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.3296A>G (p.Lys1099Arg) (rs876660132)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213461 SCV000277305 uncertain significance Hereditary cancer-predisposing syndrome 2015-07-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000799771 SCV000939449 uncertain significance Tuberous sclerosis 1 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 1099 of the TSC1 protein (p.Lys1099Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 233013). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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