Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001054097 | SCV001218393 | uncertain significance | Tuberous sclerosis 1 | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 164 of the TSC1 protein (p.Trp164Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of TSC1-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 850016). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC1 protein function. 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 | RCV003307873 | SCV003993301 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-25 | criteria provided, single submitter | clinical testing | The p.W164L variant (also known as c.491G>T), located in coding exon 4 of the TSC1 gene, results from a G to T substitution at nucleotide position 491. The tryptophan at codon 164 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |