ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.3311G>T (p.Cys1104Phe) (rs796053467)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189871 SCV000243524 uncertain significance not provided 2014-09-22 criteria provided, single submitter clinical testing p.Cys1104Phe (TGT>TTT): c.3311 G>T in exon 23 of the TSC1 gene (NM_000368.4). The C1104F variant has not been published as a mutation, nor has it been reported as a benign Polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is Not a common benign variant in these populations. The C1104F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues Differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved through mammals. In silico analysis predicts this variant is probably damaging to The protein structure/function. However, the vast majority of TSC1 mutations result in protein truncation, while missense mutations have been reported only rarely (Northrup et al., 2011; Au et Al., 2007). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000227853 SCV000284721 uncertain significance Tuberous sclerosis 1 2016-03-05 criteria provided, single submitter clinical testing This sequence change replaces cysteine with phenylalanine at codon 1104 of the TSC1 protein (p.Cys1104Phe). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TSC1-related disease. ClinVar contains an entry for this variant (Variation ID: 207648). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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