ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.89A>G (p.Lys30Arg) (rs796053452)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189831 SCV000243484 likely benign not specified 2016-12-19 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000230335 SCV000284745 uncertain significance Tuberous sclerosis 1 2018-06-15 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 30 of the TSC1 protein (p.Lys30Arg). The lysine residue is moderately 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 been reported in an individual affected 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.89A>G variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 207623). 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 arginine 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. 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.
Ambry Genetics RCV000575687 SCV000664596 uncertain significance Hereditary cancer-predisposing syndrome 2015-08-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence,In silico models in agreement (benign)

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